About this Research Topic
Cancer is a leading cause of death in the world, while tumor metastasis is responsible for about 90% of cancer-related deaths. Metastasis refers to the migration of cancer cells from their primary site to other regions of the body, which involved in local invasion, intravasation, survival in the circulation, extravasation, and colonization. The epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) were involved in tumor metastasis. EMT can help cancer cells to gain the ability of migration and invasion, which cause cancer cells to disseminate and enter new blood vessels from tumor angiogenesis. On the other hand, MET determines the colonization of disseminated tumor cells into metastatic tumors at distant organs. Another important transition of cells state is endothelial-to-mesenchymal transition (EndMT), which contributes to metastatic extravasation and intravasation. In distant organs or primary tumors, vasculature exhibits the loss of endothelial cell-cell junctions by EndMT, which causes the transendothelial migration of metastatic cells. The vasculature is lacking pericytes, the important gatekeepers against cancer progression and metastasis, in the primary tumor microenvironment. Therefore, vascular normalization could suppress tumor growth and metastasis. Once metastatic colonization has formatted, further steps are needed to start a new round of angiogenesis for feeding the new tumor. Based on the above, the critical research in a clinical context is in progress looking at both ways to treat metastases and ways to prevent this spread from the original place.
Angiogenesis is the process by which new blood vessels form, allowing the delivery of oxygen and nutrients to support the growth of tissues. In fact, angiogenesis also is a hallmark of cancer, being necessary for tumor growth and metastasis. New blood vessels provide a metastatic pathway by which tumor cells escape from the primary tumor and intravasate into the circulation system, then extravasate and set up a new nest somewhere beyond their origin. Some protein factors, signaling pathways, and non-coding RNAs participated in the entire process of angiogenesis, which included its initiation, sprouting and growth, migration, tube formation, and maturation, involving at least endothelial cells and pericytes. Cancer cells or other cells in the tumor microenvironment could secrete activating factors that stimulate the vessels to grow new extensions. With cancer, however, angiogenesis also requires inhibition of inhibitory factors. The activating factors and inhibitory factors could make up the "angiogenesis switch" to regulate tumor angiogenesis. Their balance and conversion are very important for tumor growth and metastasis. These can help to understand why cancers are more likely to metastasize to some tissues (such as the lungs, bones, liver, or brain) than others. Angiogenesis inhibitors, like everolimus, bevacizumab, sunitinib, are drugs that impede the formation of new blood vessels, hence inhibit tumor growth.
In addition, immune cells could also infiltrate into the tumor environment by new blood vessels to further coordinate angiogenesis and metastasis. For example, M2 macrophages can facilitate cancer cells by enhancing tumor angiogenesis and metastasis. However, the functions of other immune cells in angiogenesis and metastasis are still not clear. Furthermore, different cancer cells and endothelial cells possess different metastatic and angiogenic abilities respectively because of their heterogeneity, which further aggravates the complicacy of tumor angiogenesis and metastasis. Integrated analysis of single-cell RNA sequencing, bulk RNA sequencing, and spatial transcriptomics maybe illustrate systematically the mechanism of angiogenesis and tumor metastasis in spacetime dimensions to help diagnose and cure cancer.
The aim of this Research Topic is to bring together novel findings of cellular and molecular mechanisms involved in tumor angiogenesis and metastasis. Insights in the areas of intracellular and extracellular signals, tumor microenvironment, effective targeted theranostic strategies, and other investigating challenges and opportunities associated with targeting vascular are also welcome.
We would like to welcome Original Research, Review, and Mini-review articles, which will cover, but is not limited to, the following sub-topics:
1. Intracellular and extracellular signaling pathways and small molecule inhibitors in angiogenesis and tumor metastasis.
2. Molecular and cellular mechanisms of EndMT and EMT in tumor angiogenesis and metastasis.
3. Vascular normalization and metastasis in the tumor microenvironment.
4. Single-cell RNA sequencing, bulk RNA sequencing, and spatial transcriptomics for angiogenesis and tumor metastasis.
5. Regulatory roles of non-coding RNAs and exosomes in angiogenesis and tumor metastasis.
6. Regulatory roles of immune cells for angiogenesis and metastasis in the tumor microenvironment.
7. Biomarker and targets of diagnoses and treatment for angiogenesis and tumor metastasis.
8. Animal models for in vivo imaging and quantification of angiogenesis and tumor metastasis.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Keywords: Tumor metastasis, Angiogenesis, RNA sequencing, EndMT and EMT, Biomarker
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.