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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00724

Elevated expression levels of PC3-secreted microprotein (PSMP) in prostate cancer associated with increased xenograft growth and modification of immune-related microenvironment

 Xiaolei Pei1,  Danfeng Zheng2, Zhiwei Fang3,  Shiying Zhang3, Hao Hu3*, Kexin Xu3 and  Ying Wang4
  • 1Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China
  • 2Southeast University, China
  • 3Peking University People's Hospital, China
  • 4Peking University Health Science Centre, China

Prostate cancer (PCa), especially metastatic PCa, is one of the main cancer types accounting for male mortality worldwide. Over decades, researchers have tried to search for effective curative methods for PCa, but many attempts have failed. The therapeutic failure of PCa is usually due to off-target or side effects; thus, finding a key molecule that could prevent PCa metastatic progression has become the most important goal for curing aggressive PCa. In this study, we collected hundreds of PCa tissues and serum and urine samples from patients to verify the upregulated expression of PSMP in PCa tumor tissues with high Gleason scores. According to biopsies result, PSMP expression was found related to extraprostatic extension (EPE), contributing to PCa metastasis. Mechanistically, recombinant PSMP protein could promote the proliferation both in vitro and in vivo, and rhPSMP could promote epithelial-mesenchymal transition of PC3 in vitro. Additionally, PSMP could also influence the cytokines production in a xenograft model and monocyte migration and macrophage polarization in vitro. Our most important finding was that neutralizing antibodies against PSMP could suppress xenograft PC3 growth and promote the survival of PC3 metastatic mice model, might provide an effective option to cure human PCa.

Keywords: prostate cancer, PSMP, Therapeutic target, neutralizing antibody, microenvironment

Received: 10 Apr 2019; Accepted: 22 Jul 2019.

Edited by:

Kuzhuvelil B. Harikumar, Rajiv Gandhi Centre for Biotechnology, India

Reviewed by:

Kamini Singh, Memorial Sloan Kettering Cancer Center, United States
Vijay Pandey, Tsinghua-Berkeley Shenzhen Institute, China  

Copyright: © 2019 Pei, Zheng, Fang, Zhang, Hu, Xu 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: Mx. Hao Hu, Peking University People's Hospital, Beijing, 100044, China, pkuxiaolei@sina.com