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MINI REVIEW article

Front. Genet., 04 July 2018 | https://doi.org/10.3389/fgene.2018.00232

Pre-clinical Models for Malignant Mesothelioma Research: From Chemical-Induced to Patient-Derived Cancer Xenografts

Noushin Nabavi1,2, Jingchao Wei1,3, Dong Lin1,2, Colin C. Collins1, Peter W. Gout2 and Yuzhuo Wang1,2*
  • 1Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada
  • 2Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, Canada
  • 3Department of Urology, the Third Xiangya Hospital, Central South University, Changsha, China

Malignant mesothelioma (MM) is a rare disease often associated with environmental exposure to asbestos and other erionite fibers. MM has a long latency period prior to manifestation and a poor prognosis. The survival post-diagnosis is often less than a year. Although use of asbestos has been banned in the United States and many European countries, asbestos is still being used and extracted in many developing countries. Occupational exposure to asbestos, mining, and migration are reasons that we expect to continue to see growing incidence of mesothelioma in the coming decades. Despite improvements in survival achieved with multimodal therapies and cytoreductive surgeries, less morbid, more effective interventions are needed. Thus, identifying prognostic and predictive biomarkers for MM, and developing novel agents for targeted therapy, are key unmet needs in mesothelioma research and treatment. In this review, we discuss the evolution of pre-clinical model systems developed to study MM and emphasize the remarkable capability of patient-derived xenograft (PDX) MM models in expediting the pre-clinical development of novel therapeutic approaches. PDX disease model systems retain major characteristics of original malignancies with high fidelity, including molecular, histopathological and functional heterogeneities, and as such play major roles in translational research, drug development, and precision medicine.

Introduction

Malignant mesothelioma (MM) as a rare disease occurs infrequently in the general population, typically affecting fewer than 3,000 patients in North America (Bianchi and Bianchi, 2014). The pleural form, affecting the lining of the chest cavity and lungs, is often referred to as a man-made disease due to high correlation of incidence with exposure to asbestos. The rarer form affecting the abdominal cavity, i.e., peritoneal mesothelioma (PeM), is more common in women and is often subject to incorrect diagnosis (Alakus et al., 2015; Shin and Kim, 2016). Additionally, aside from a few large scale-studies on pleural mesothelioma (PM) (Zhang et al., 2015; Bueno et al., 2016; Joseph et al., 2017), PeM remains largely unexplored. Like many known rare diseases, mesotheliomas have no approved targeted therapy and cisplatin-pemetrexed chemotherapy remains the standard of care (van Zandwijk et al., 2013). MM is frequently acute and life-threatening, with survival of less than 1 year in the majority of cases. While large numbers of people may have been exposed to asbestos through occupational or domestic exposure, significantly smaller numbers go on to develop mesothelioma (Carbone et al., 2012), suggesting the involvement of genomic predispositions in disease development. For instance, recent genomic profiling of mesotheliomas shows that mutations in the BAP1 gene render its protein product inactive, and are correlated with MM and uveal melanoma incidence (Testa et al., 2011; Alakus et al., 2015; Ji et al., 2016). Whereas more research is needed to understand other genetic links to MM tumorigenesis, progress is exacerbated by its existential paradox, lack of funding, disease model systems and research resources. Next-generation sequencing technologies (ChIP-Seq, RNA-Seq, DNA-Seq, and Proteome-Seq) applied to patient-derived cell and animal models in rare disease research are becoming key venues to identify the underlying etiology of the disease. Here we review the past and current pre-clinical models in MM research (see Supplementary Table S1) and address some of the challenges, limitations, and opportunities that can advance its status quo.

Historical Development of Mm Models Through Chemical Induction and Gene Modification

It is well-established that chronic exposure to asbestos induces development of human pleural mesothelial cells with cancer-like properties (Lohcharoenkal et al., 2013). Clinically, it has been demonstrated that exposure to asbestos causes many lung diseases such as asbestosis, MM, and lung cancer due to the generation of chromosomal damage and DNA aberrations (Nymark et al., 2007). Historically, to study tumorigenesis of MM, animal and cell models were induced through exposure to varying doses and sizes of asbestos fibers (Whitaker et al., 1984; Topov and Kolev, 1987; Davis et al., 1992; Pass and Mew, 1996) by intrapleural or intraperitoneal injection of asbestos fibers into laboratory rats, mice, or hamsters or incubation of normal mesothelial cell lines with the fibers. Potential MM models would eventually manifest following long latency periods of approximately 7 months for mice, 12 months for rats, and years for primates (Suzuki, 1991). Although these models are difficult to develop, they are ideal platforms for testing and selecting new combinations or targeted therapies, or studying de novo carcinogenic pathways.

Prior to the turn of this century, Simian virus 40 (SV40) was another identified agent widely studied to induce MM (Testa et al., 1998; Bocchetta et al., 2000). Although it is controversial that SV40 contributes to the development of mesothelioma as a causative factor (Hubner and Van Marck, 2002; López-Ríos et al., 2004), its role as a cofactor with asbestos has been established in animal models. Interestingly, some studies showed that SV40 rendered animals more susceptible to asbestos-related carcinogenesis (Kroczynska et al., 2006; Robinson et al., 2006), while asbestos was also reported to promote SV40 infection of cells (Appel et al., 1988).

Following chemical induction of MM, novel genetic models were generated to understand genomic predispositions to this malignancy independent of exposure to asbestos (Jongsma et al., 2008). Both knock-out and knock-in animal models are meaningful steps forward in research and are particularly useful for showing the potential importance of a single gene in disease progression. Well-established genetic studies associated with MM include loss of p16INK4A, p14ARF, Nf2, p53 and possibly Rb (Cheng et al., 1994; Bianchi et al., 1995; Mor et al., 1997; Papp et al., 2001). Additional studies showed that Nf2 is one of the most frequently mutated tumor suppressor genes in PeM (Sekido et al., 1995), and that asbestos-exposed Nf2 knockout mice exhibited accelerated MM tumor formation (Altomare et al., 2005). To demonstrate the powerful effect of Nf2 deficiency in inducing MM, Nf2-deficient mice were crossed with either Ink4a/Arf-deficient or p53-deficient mice, and in the absence of any exposure to asbestos, a high incidence of short median survival of invasive pleural mesothelioma developed (Altomare et al., 2005; Jongsma et al., 2008). Combined genomics studies further showed that MM tumors have frequent hypermethylations or deletions at the Cdkn2a/Arf and Cdkn2b gene loci (Kane, 2006). In summary, in combination with patient-derived xenografts, these models are invaluable systems for studying chronic and systemic effects of gene aberration burden in MM development and deciphering clear linkages between asbestos exposure and genetic predisposition.

Patient-Derived Cell Models of Mm Accelerating Research and Development

Patient-derived cell lines in MM have served as impactful tools for profiling gene expressions, excavating new asbestos-associated genes and pathways, and identifying chromosomal regions that contribute to asbestos and therapy responses. Common chromosomal abnormalities, such as deletions, of chromosomes 1, 3, 4, 9, 11, 14 and 22, have been identified in patient-derived cell lines of MM (Popescu et al., 1988; Taguchi et al., 1993; Lee et al., 1996). Additionally, asbestos-affected genetic pathways such as integrin-mediated signaling pathways, MAPK pathways, and NFKB/IKB pathways (Ramos-Nino et al., 2003) can be attributed to advances brought about by patient-derived cell lines.

These developments started historically as early as 1982 in a study that reported a first-in-field in vitro patient-derived mesothelioma cell line that was generated from abdominal fluid of a patient diagnosed with mesothelioma. It was shown that this cell line stably yielded MM up to 100 passages (Behbehani et al., 1982). Subsequently, an H-MESO-1 cell line was derived from a 35-years old male diagnosed with MM (Reale et al., 1987); it was capable of growing both as nodules and as ascitic fluid with peritoneal seeding and diffuse peritoneal thickening, strongly mimicking the growth pattern of this tumor type in humans (Reale et al., 1987). Subsequently, a panel of 17 human MM cell lines was derived from 61 patients (46 effusions, 9 biopsies, and 6 tumors obtained at autopsy) and 5 of these cell lines were characterized to closely recapitulate human disease (Wu et al., 1985; Versnel et al., 1989; Tange et al., 1995). Interestingly, Ishiwata et al. (2003) derived a cell line termed HMMME in 2003 from the pleural fluids of a MM case that grew well, both in vitro and in vivo, with a doubling time of 42 h, without interruption for 12 years, and was sub-cultured over 200 times. Following these advances, Usami et al. (2006) established and characterized additional malignant PM cell lines (ACC-MESO-1, ACC-MESO-4, Y-MESO-8A, and Y-MESO-8D), and detected differentially expressed genes between Y-MESO-8A and Y-MESO-8D, which were derived from the same patient. Among these four cell lines, Nf2 was found to be mutated only in ACC-MESO-1. This is an important finding as exploring the genomic aberrations associated of cells is necessary to testing potential targeted therapies and to better translate research discoveries. A search of clinicaltrials.gov in order to find clinical trials treating NF2 mutated solid tumors in patients suggests Everolimus, an oral derivative of rapamycin (NCT02352844) which is in phase 2 of trials, may be a potential targeted therapy to test in these cells. In another study, homozygous deletions of p16INK4A and inactivation of the p14ARF gene were found in all four cell lines. Again, the NCT02688907 phase 2 clinical trial recruiting small cell lung-cancer patients with a p16INK4A mutation uses AZD1775, a tyrosine kinase inhibitor. In vitro studies with this inhibitor in relevant MM cell lines as such can accelerate pre-clinical developments. Additionally, a key advancement in the field was the establishment of three PM cell lines (TCC-MESO-1, TCC-MESO-2, and TCC-MESO-3) by Yanagihara et al. (2010) from primary and metastatic tumors of a patient with epithelioid subtype and 1 line from a mixed tumor subtype (epithelioid and sarcomatoid) allowing for pathological subtype investigations both in vitro and in vivo. Traditional cell culture technologies such as gene transfections can be widely applied to malignant cells to directly study mechanisms of pathogenesis and tumorigenesis. However, cells in multicellular spheroids can mimic resistance to drugs better than monolayer cells as they preserve the complexity of the original tumor (Yanagihara et al., 2010). Thus, discovering genomic aberrations in these cell lines further enables the assessment and development of pre-clinical targeted therapeutics. One example utilizing testing drugs on patient-derived cell lines is a study confirming the successful response of a 3D multicellular spheroids of MM (MSTO-211H) to cytotoxic Paclitaxel-loaded nanoparticles (Lei et al., 2015). Appreciating the numerous advantages of cell lines in pre-clinical research, they are not without their shortcomings some of which include inability to precisely reflect in vivo conditions such as heterogeneities and tumor microenvironment. Thus, they necessitate further validation in models that better mimic intratumoral parameters of human disease.

Patient-Derived Animal Models of Mm for Pre-Clinical Research and Development

The practice of engrafting tumor fragments from patient surgical tissues or biopsies either heterotopically or orthotopically in immunodeficient mice started in the 1950s (Woolley, 1958). Heterotopical implants occur when the tumor fragments are implanted into mice unrelated to the original tumor site, generally in the subcutaneous site, or sometimes in sub-renal capsular sites. Both of these models are unique in answering specific questions and are invaluable tools for mesothelioma research. Subcutaneous tissue xenografts rarely produce metastasis in mice, and have engraftment success rates of 40–60%, whereas sub-renal capsule tissue xenografts maintain the original tumor stroma (at least in the first generation) as well as the host stroma and have engraftment success rates of 95% (Wang et al., 2017). Knowing this, the mesothelioma field has attempted many of these techniques with remarkable success. For instance, Arnold colleagues for the first time reported inoculation of mesothelioma cells into nude mice to establish an in vivo mesothelioma xenograft model in Arnold et al. (1979) and Nissen et al. (1979). Later, Chahinian et al. (1980) successfully established six such xenografts by subcutaneous inoculation of fresh tumor specimens into nude mice. To investigate the suitability of MM PDX models in pre-clinical studies, tumors from 50 patients were implanted into immunodeficient mice and serially passaged for up to five generations (Wu et al., 2017). Successful PDXs were formed in 20 of 50 (40%) tumors implanted retaining both the morphology and characteristic genotypic and phenotypic markers of the primary lesion. Interestingly, PDX formation was associated with poor survival of the patients, making them ideal and replicable models to identify prognostic biomarkers and/or develop better pre-clinical therapeutic strategies. Interestingly, PDX models derived from epithelioid and sarcomatoid pathologies of mesothelioma have similar differentiation states as the original tumors (Darai-Ramqvist et al., 2013). The sarcomatoid mesothelioma subtype present with a faster growth rate than the epithelioid subtype in PDXs, consistent with its aggressive physiological behavior in humans (Darai-Ramqvist et al., 2013). The different growth patterns in mixed type mesotheliomas are suitably replicated in PDXs, making them invaluable models for investigating MM’s cell differentiation, heterogeneity, and tumor evolution. In another study, mesothelioma cells isolated from ascites or pleural fluid of mesothelioma patients were injected into nude/SCID mice to generate PDX models. All PDXs exhibited morphologic and immunohistochemical features consistent with those of original patients’ mesothelioma cells (Kalra et al., 2015). Since these models provide biological incubators for inoculated tumors, they provide a tumor repository platform that allows deep genomic and pathological analyses. For instance, it was found in this study that BAP1 loss correlated with enhanced tumor growth. Similar to human cells, murine mesothelioma cells injected into humanized BALB/c mice allow study of tumor cell interaction with the immune system. In one study, murine mesothelioma cells responded to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator (Mezzapelle et al., 2016). Other malignant mesothelioma cell lines, TCC-MESO-1, TCC-MESO-2 and TCC-MESO-3, show tumorigenicity in mice after orthotopic implantation (Yanagihara et al., 2010) and allow evaluation of anticancer agents in vivo (Opitz et al., 2007; Yanagihara et al., 2010). Thus, establishment of PDX models of MM in immunocompromised mice provides a high-fidelity model with minimal genetic drift and physiologically relevant tumor microenvironments to investigate the etiology of this malignancy and develop new therapeutic agents for MM. Here, we hope to shed light on the concept that PDXs in combination with emerging gene-editing or nano-particle therapeutic techniques are paramount to harnessing the full potential of animal models. To our surprise, however, animal studies that take into account the genomic background of MMs for targeted therapy explorations are very limited. We think integrating the knowledge from genomic aberrations of MM models with targeted therapeutics for those aberrations can be largely utilized in mesothelioma research and have the potential for illuminating the value of these models in answering critical and unmet research needs. Some of the unexplored capabilities that these MM PDX models provide include expediting targeted therapy efficacies and accelerating pre-clinical translation of novel therapeutic approaches from other indications and applying them to MM.

Conclusion

Our understanding of MM biology is hindered by its slow onset, low prevalence, and difficulties of manifesting prolonged predisposing conditions to induce lesions in model systems. While historical models need yet to faithfully recapitulate all aspects of the clinical disease, MM PDX models are remarkable systems that enable insights into the genetics of tumor initiation, growth, and metastasis. In this review, we provide an overview of the major known models in the mesothelioma field that have been instrumental in key discoveries in the past century. We also highlight unresolved questions and limitations that hamper translational progress. We argue that although PDX models come with inherent challenges such as cost, failing to graft in vitro or in vivo, or not efficiently translating to clinical protocols, they are invaluable platforms to investigate the underlying mechanisms driving tumor initiation, progression, metastatic events, as well as therapeutic interventions. Conventional orthotopic, sub-renal, and subcutaneous transplantation models as well as cell lines remain indispensable in continuing the study of MM and new models that can spontaneously develop mesothelioma and be used to test novel and targeted agents are current clinically unmet needs.

Author Contributions

NN, JW, DL, PG, CC, and YW: conception. NN, JW, DL, and PG: writing, review, and/or revision of the manuscript. CC and YW: study supervision.

Funding

This work was supported by the Canadian Institutes of Health Research (YW), BC Cancer Foundation Mesothelioma Research Fund/Mitacs Accelerate Postdoctoral Fellowship Fund (NN, YW, and CC), and the Terry Fox New Frontiers Program on Prostate Cancer Progression (CC and YW). JW’s work is supported by visiting scholarships from China Scholar Council to JW (#201706370135).

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Supplementary Material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fgene.2018.00232/full#supplementary-material

TABLE S1 | Summary of pre-clinical models used for malignant mesothelioma research.

References

Alakus, H., Yost, S. E., Woo, B., French, R., Lin, G. Y., Jepsen, K., et al. (2015). BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma. J. Transl. Med. 13:122. doi: 10.1186/s12967-015-0485-1

PubMed Abstract | CrossRef Full Text | Google Scholar

Altomare, D. A., Vaslet, C. A., Skele, K. L., De Rienzo, A., Devarajan, K., Jhanwar, S. C., et al. (2005). A mouse model recapitulating molecular features of human mesothelioma. Cancer Res. 65, 8090–8095. doi: 10.1158/0008-5472.CAN-05-2312

PubMed Abstract | CrossRef Full Text | Google Scholar

Appel, J. D., Fasy, T. M., Kohtz, D. S., Kohtz, J. D., and Johnson, E. M. (1988). Asbestos fibers mediate transformation of monkey cells by exogenous plasmid DNA. Proc. Natl. Acad. Sci. U.S.A. 85, 7670–7674. doi: 10.1073/pnas.85.20.7670

PubMed Abstract | CrossRef Full Text | Google Scholar

Arnold, W., Naundorf, H., Wildner, G. P., Nissen, E., and Tanneberger, S. (1979). Biological characterization of a mesothelioma line in nude mice. I. Transplantation of in vitro cultivated cells of a human ascitic tumor effusion. Arch. Geschwulstforsch. 49, 495–507.

PubMed Abstract | Google Scholar

Behbehani, A. M., Hunter, W. J., Chapman, A. L., and Lin, F. (1982). Studies of a human mesothelioma. Hum. Pathol. 13, 862–866. doi: 10.1016/S0046-8177(82)80083-X

CrossRef Full Text | Google Scholar

Bianchi, A. B., Mitsunaga, S. I., Cheng, J. Q., Klein, W. M., Jhanwar, S. C., Seizinger, B., et al. (1995). High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas. Proc. Natl. Acad. Sci. U.S.A. 92, 10854–10858. doi: 10.1073/pnas.92.24.10854

PubMed Abstract | CrossRef Full Text | Google Scholar

Bianchi, C., and Bianchi, T. (2014). Global mesothelioma epidemic: trend and features. Indian J. Occup. Environ. Med. 18, 82–88. doi: 10.4103/0019-5278.146897

PubMed Abstract | CrossRef Full Text | Google Scholar

Bocchetta, M., Di Resta, I., Powers, A., Fresco, R., Tosolini, A., Testa, J. R., et al. (2000). Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity. Proc. Natl. Acad. Sci. U.S.A. 97, 10214–10219. doi: 10.1073/pnas.170207097

PubMed Abstract | CrossRef Full Text | Google Scholar

Bueno, R., Stawiski, E. W., Goldstein, L. D., Durinck, S., De Rienzo, A., Modrusan, Z., et al. (2016). Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat. Genet. 48, 407–416. doi: 10.1038/ng.3520

PubMed Abstract | CrossRef Full Text | Google Scholar

Carbone, M., Ly, B. H., Dodson, R. F., Pagano, I., Morris, P. T., Dogan, U. A., et al. (2012). Malignant mesothelioma: facts, myths, and hypotheses. J. Cell. Physiol. 227, 44–58. doi: 10.1002/jcp.22724

PubMed Abstract | CrossRef Full Text | Google Scholar

Chahinian, A. P., Beranek, J. T., Suzuki, Y., Bekesi, J. G., Wisniewski, L., Selikoff, I. J., et al. (1980). Transplantation of human malignant mesothelioma into nude mice. Cancer Res. 40, 181–185.

Google Scholar

Cheng, J. Q., Jhanwar, S. C., Klein, W. M., Bell, D. W., Lee, W. C., Altomare, D. A., et al. (1994). p16 alterations and deletion mapping of 9p21-p22 in malignant mesothelioma. Cancer Res. 54, 5547–5551.

PubMed Abstract | Google Scholar

Darai-Ramqvist, E., Nilsonne, G., Flores-Staino, C., Hjerpe, A., and Dobra, K. (2013). Microenvironment-dependent phenotypic changes in a SCID mouse model for malignant mesothelioma. Front. Oncol. 3:203. doi: 10.3389/fonc.2013.00203

PubMed Abstract | CrossRef Full Text | Google Scholar

Davis, M. R., Manning, L. S., Whitaker, D., Garlepp, M. J., and Robinson, B. W. (1992). Establishment of a murine model of malignant mesothelioma. Int. J. Cancer 52, 881–886. doi: 10.1002/ijc.2910520609

CrossRef Full Text | Google Scholar

Hubner, R., and Van Marck, E. (2002). Reappraisal of the strong association between simian virus 40 and human malignant mesothelioma of the pleura (Belgium). Cancer Causes Control 13, 121–129. doi: 10.1023/A:1014321729038

PubMed Abstract | CrossRef Full Text | Google Scholar

Ishiwata, I., Ishiwata, C., Anzo, M., Minami, R., Kiguchi, K., Tachibana, T., et al. (2003). Establishment and characterization of a human malignant mesothelioma cell line (HMMME). Hum. Cell 16, 231–239. doi: 10.1111/j.1749-0774.2003.tb00157.x

PubMed Abstract | CrossRef Full Text | Google Scholar

Ji, J., Sundquist, J., and Sundquist, K. (2016). Incidence and familial risk of pleural mesothelioma in Sweden: a national cohort study. Eur. Respir. J. 48, 873–879. doi: 10.1183/13993003.00091-2016

PubMed Abstract | CrossRef Full Text | Google Scholar

Jongsma, J., van Montfort, E., Vooijs, M., Zevenhoven, J., Krimpenfort, P., van der Valk, M., et al. (2008). A conditional mouse model for malignant mesothelioma. Cancer Cell 13, 261–271. doi: 10.1016/j.ccr.2008.01.030

PubMed Abstract | CrossRef Full Text | Google Scholar

Joseph, N. M., Chen, Y.-Y., Nasr, A., Yeh, I., Talevich, E., Onodera, C., et al. (2017). Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X. Mod. Pathol. 30, 246–254. doi: 10.1038/modpathol.2016.188

PubMed Abstract | CrossRef Full Text | Google Scholar

Kalra, N., Zhang, J., Thomas, A., Xi, L., Cheung, M., Talarchek, J., et al. (2015). Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that mimic the molecular characteristics of human malignant mesothelioma. BMC Cancer 15:376. doi: 10.1186/s12885-015-1362-2

PubMed Abstract | CrossRef Full Text | Google Scholar

Kane, A. B. (2006). Animal models of malignant mesothelioma. Inhal. Toxicol. 18, 1001–1004. doi: 10.1080/08958370600835393

PubMed Abstract | CrossRef Full Text | Google Scholar

Kroczynska, B., Cutrone, R., Bocchetta, M., Yang, H., Elmishad, A. G., Vacek, P., et al. (2006). Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters. Proc. Natl. Acad. Sci. U.S.A. 103, 14128–14133. doi: 10.1073/pnas.0604544103

PubMed Abstract | CrossRef Full Text | Google Scholar

Lee, W. C., Balsara, B., Liu, Z., Jhanwar, S. C., and Testa, J. R. (1996). Loss of heterozygosity analysis defines a critical region in chromosome 1p22 commonly deleted in human malignant mesothelioma. Cancer Res. 56, 4297–4301.

PubMed Abstract | Google Scholar

Lei, H., Hofferberth, S. C., Liu, R., Colby, A., Tevis, K. M., Catalano, P., et al. (2015). Paclitaxel-loaded expansile nanoparticles enhance chemotherapeutic drug delivery in mesothelioma 3-dimensional multicellular spheroids. J. Thorac. Cardiovasc. Surg. 149, 1417–1424; discussion 1424.e1–1425.e1. doi: 10.1016/j.jtcvs.2015.02.020

PubMed Abstract | CrossRef Full Text | Google Scholar

Lohcharoenkal, W., Wang, L., Stueckle, T. A., Dinu, C. Z., Castranova, V., Liu, Y., et al. (2013). Chronic exposure to carbon nanotubes induces invasion of human mesothelial cells through matrix metalloproteinase-2. ACS Nano 7, 7711–7723. doi: 10.1021/nn402241b

PubMed Abstract | CrossRef Full Text | Google Scholar

López-Ríos, F., Illei, P. B., Rusch, V., and Ladanyi, M. (2004). Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids. Lancet 364, 1157–1166. doi: 10.1016/S0140-6736(04)17102-X

PubMed Abstract | CrossRef Full Text | Google Scholar

Mezzapelle, R., Rrapaj, E., Gatti, E., Ceriotti, C., Marchis, F. D., Preti, A., et al. (2016). Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells. Sci. Rep. 6:22850. doi: 10.1038/srep22850

PubMed Abstract | CrossRef Full Text | Google Scholar

Mor, O., Yaron, P., Huszar, M., Yellin, A., Jakobovitz, O., Brok-Simoni, F., et al. (1997). Absence of p53 mutations in malignant mesotheliomas. Am. J. Respir. Cell Mol. Biol. 16, 9–13. doi: 10.1165/ajrcmb.16.1.8998073

PubMed Abstract | CrossRef Full Text | Google Scholar

Nissen, E., Arnold, W., Weiss, H., Naundorf, H., and Tanneberger, S. (1979). Biological characterization of a mesothelioma line in the nude mice. II. Some characteristics of cells cultivated in vitro prior to and after transplantation in nude mice. Arch. Geschwulstforsch. 49, 544–550.

PubMed Abstract | Google Scholar

Nymark, P., Lindholm, P. M., Korpela, M. V., Lahti, L., Ruosaari, S., Kaski, S., et al. (2007). Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines. BMC Genomics 8:62. doi: 10.1186/1471-2164-8-62

PubMed Abstract | CrossRef Full Text | Google Scholar

Opitz, I., Lardinois, D., Arni, S., Hillinger, S., Vogt, P., Odermatt, B., et al. (2007). Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment. Eur. J. Cardiothorac. Surg. 31, 773–778. doi: 10.1016/j.ejcts.2007.01.047

PubMed Abstract | CrossRef Full Text | Google Scholar

Papp, T., Schipper, H., Pemsel, H., Bastrop, R., Muller, K. M., Wiethege, T., et al. (2001). Mutational analysis of N-ras, p53, p16INK4a, p14ARF and CDK4 genes in primary human malignant mesotheliomas. Int. J. Oncol. 18, 425–433. doi: 10.3892/ijo.18.2.425

PubMed Abstract | CrossRef Full Text | Google Scholar

Pass, H. I., and Mew, D. J. (1996). In vitro and in vivo studies of mesothelioma. J. Cell. Biochem. Suppl. 24, 142–151. doi: 10.1002/jcb.240630509

CrossRef Full Text | Google Scholar

Popescu, N. C., Chahinian, A. P., and DiPaolo, J. A. (1988). Nonrandom chromosome alterations in human malignant mesothelioma. Cancer Res. 48, 142–147.

Google Scholar

Ramos-Nino, M. E., Heintz, N., Scappoli, L., Martinelli, M., Land, S., Nowak, N., et al. (2003). Gene profiling and kinase screening in asbestos-exposed epithelial cells and lungs. Am. J. Respir. Cell Mol. Biol. 29(Suppl. 3), S51–S58.

PubMed Abstract | Google Scholar

Reale, F. R., Griffin, T. W., Compton, J. M., Graham, S., Townes, P. L., and Bogden, A. (1987). Characterization of a human malignant mesothelioma cell line (H-MESO-1): a biphasic solid and ascitic tumor model. Cancer Res. 47, 3199–3205.

PubMed Abstract | Google Scholar

Robinson, C., van Bruggen, I., Segal, A., Dunham, M., Sherwood, A., Koentgen, F., et al. (2006). A novel SV40 TAg transgenic model of asbestos-induced mesothelioma: malignant transformation is dose dependent. Cancer Res. 66, 10786–10794. doi: 10.1158/0008-5472.CAN-05-4668

PubMed Abstract | CrossRef Full Text | Google Scholar

Sekido, Y., Pass, H. I., Bader, S., Mew, D. J., Christman, M. F., Gazdar, A. F., et al. (1995). Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Cancer Res. 55, 1227–1231.

PubMed Abstract | Google Scholar

Shin, H. D., and Kim, S. B. (2016). Benign cystic mesothelioma misdiagnosed as peritoneal carcinomatosis. Case Rep. Gastroenterol. 10, 115–120. doi: 10.1159/000444445

PubMed Abstract | CrossRef Full Text | Google Scholar

Suzuki, Y. (1991). Comparability of mesothelioma in humans and in experimental animal studies. Ann. N. Y. Acad. Sci. 643, 219–222. doi: 10.1111/j.1749-6632.1991.tb24465.x

PubMed Abstract | CrossRef Full Text | Google Scholar

Taguchi, T., Jhanwar, S. C., Siegfried, J. M., Keller, S. M., and Testa, J. R. (1993). Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma. Cancer Res. 53, 4349–4355.

Google Scholar

Tange, T., Hasegawa, Y., Oka, T., Sunaga, S., Higashihara, M., Matsuo, K., et al. (1995). Establishment and characterization of a new human mesothelioma cell line (T-85) from malignant peritoneal mesothelioma with remarkable thrombocytosis. Pathol. Int. 45, 791–800. doi: 10.1111/j.1440-1827.1995.tb03399.x

PubMed Abstract | CrossRef Full Text | Google Scholar

Testa, J. R., Carbone, M., Hirvonen, A., Khalili, K., Krynska, B., Linnainmaa, K., et al. (1998). A multi-institutional study confirms the presence and expression of simian virus 40 in human malignant mesotheliomas. Cancer Res. 58, 4505–4509.

PubMed Abstract | Google Scholar

Testa, J. R., Cheung, M., Pei, J., Below, J. E., Tan, Y., Sementino, E., et al. (2011). Germline BAP1 mutations predispose to malignant mesothelioma. Nat. Genet. 43, 1022–1025. doi: 10.1038/ng.912

PubMed Abstract | CrossRef Full Text | Google Scholar

Topov, J., and Kolev, K. (1987). Cytology of experimental mesotheliomas induced with crocidolite asbestos. Acta Cytol. 31, 369–373.

Google Scholar

Usami, N., Fukui, T., Kondo, M., Taniguchi, T., Yokoyama, T., Mori, S., et al. (2006). Establishment and characterization of four malignant pleural mesothelioma cell lines from Japanese patients. Cancer Sci. 97, 387–394. doi: 10.1111/j.1349-7006.2006.00184.x

PubMed Abstract | CrossRef Full Text | Google Scholar

van Zandwijk, N., Clarke, C., Henderson, D., Musk, A. W., Fong, K., Nowak, A., et al. (2013). Guidelines for the diagnosis and treatment of malignant pleural mesothelioma. J. Thorac. Dis. 5, E254–E307.

Google Scholar

Versnel, M. A., Bouts, M. J., Hoogsteden, H. C., van der Kwast, T. H., Delahaye, M., and Hagemeijer, A. (1989). Establishment of human malignant mesothelioma cell lines. Int. J. Cancer 44, 256–260. doi: 10.1002/ijc.2910440212

CrossRef Full Text | Google Scholar

Wang, Y., Lin, D., and Gout, P. W. (eds). (2017). Patient-Derived Xenograft Models of Human Cancer. Berlin: Springer. doi: 10.1007/978-3-319-55825-7

CrossRef Full Text | Google Scholar

Whitaker, D., Shilkin, K. B., and Walters, M. N. (1984). Cytologic and tissue culture characteristics of asbestos-induced mesothelioma in rats. Acta Cytol. 28, 185–189.

PubMed Abstract | Google Scholar

Woolley, G. W. (1958). Discussion of part VI. Ann. N. Y. Acad. Sci. 76, 821–825. doi: 10.1111/j.1749-6632.1958.tb54899.x

CrossRef Full Text | Google Scholar

Wu, L., Allo, G., John, T., Li, M., Tagawa, T., Opitz, I., et al. (2017). Patient-derived xenograft establishment from human malignant pleural mesothelioma. Clin. Cancer Res. 23, 1060–1067. doi: 10.1158/1078-0432.CCR-16-0844

PubMed Abstract | CrossRef Full Text | Google Scholar

Wu, S. F., Wang, E. Z., Su, J. Z., Xu, H. X., Lin, Z. Q., Sheng, C. F., et al. (1985). Establishment and characterization of human malignant pleural mesothelioma cell line SMC-1. Sci. Sin. B 28, 281–288.

PubMed Abstract | Google Scholar

Yanagihara, K., Tsumuraya, M., Takigahira, M., Mihara, K., Kubo, T., Ohuchi, K., et al. (2010). An orthotopic implantation mouse model of human malignant pleural mesothelioma for in vivo photon counting analysis and evaluation of the effect of S-1 therapy. Int. J. Cancer 126, 2835–2846. doi: 10.1002/ijc.25002

PubMed Abstract | CrossRef Full Text | Google Scholar

Zhang, W., Wu, X., Wu, L., Zhang, W., and Zhao, X. (2015). Advances in the diagnosis, treatment and prognosis of malignant pleural mesothelioma. Ann. Transl. Med. 3:182. doi: 10.3978/j.issn.2305-5839.2015.07.03

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: rare diseases, genomics, patient-derived xenografts, malignant mesothelioma, pre-clinical cancer research, drug development

Citation: Nabavi N, Wei J, Lin D, Collins CC, Gout PW and Wang Y (2018) Pre-clinical Models for Malignant Mesothelioma Research: From Chemical-Induced to Patient-Derived Cancer Xenografts. Front. Genet. 9:232. doi: 10.3389/fgene.2018.00232

Received: 05 March 2018; Accepted: 11 June 2018;
Published: 04 July 2018.

Edited by:

Amritha Jaishankar, Rare Genomics Institute, United States

Reviewed by:

Theodora Katsila, University of Patras, Greece
Vita Dolzan, University of Ljubljana, Slovenia

Copyright © 2018 Nabavi, Wei, Lin, Collins, Gout and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Yuzhuo Wang, ywang@bccrc.ca