Journal
JOURNAL OF CELL SCIENCE
Volume 122, Issue 11, Pages 1723-1736Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.030197
Keywords
Semaphorins; Plexins; Tumor; Tumor microenvironment
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Funding
- Italian Association for Cancer Research (AIRC) and Regione Piemonte
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Semaphorins are a large family of secreted and membrane-bound molecules that were initially implicated in the development of the nervous system and in axon guidance. More recently, they have been found to regulate cell adhesion and motility, angiogenesis, immune responses, and tumor progression. Semaphorin receptors, the neuropilins and the plexins, are expressed by a wide variety of cell types, including endothelial cells, bone-marrow-derived cells and cancer cells. Interestingly, a growing body of evidence indicates that semaphorins also have an important role in cancer. It is now known that cancer progression, invasion and metastasis involve not only genetic changes in the tumor cells but also crosstalk between tumor cells and their surrounding non-tumor cells. Through the recruitment of endothelial cells, leukocytes, pericytes and fibroblasts, and the local release of growth factors and cytokines, the tumor microenvironment can mediate tumor-cell survival, tumor proliferation and regulation of the immune response. Moreover, by conferring cancer cells with an enhanced ability to migrate and invade adjacent tissues, extracellular regulatory signals can play a major role in the metastatic process. In this Commentary, we focus on the emerging role of semaphorins in mediating the crosstalk between tumor cells and multiple stromal cell types in the surrounding microenvironment.
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