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. 2019 Feb 18;7:16. doi: 10.3389/fcell.2019.00016

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Copyright © 2019 Turdo, Veschi, Gaggianesi, Chinnici, Bianca, Todaro and Stassi.

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.

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Tumor angiogenesis and metastatic process. Cancer cells secrete pro-angiogenic and pro-tumorigenic factors (MMPs, VEGF-A, HIF-1A, cytokines, chemokines, growth factors). VEGF-A activates endothelial cells (ECs) in tip cells, that direct the sprouting vessels, and stalk cells, implicated in vessel stability. Moreover, cancer cells-released cytokines activate cancer-associated fibroblasts (CAFs) and activated tumor-associated macrophages (TAMs), that in turn favor the intravasation of cancer stem cells (CSCs). Circulating cancer cells (CTCs) through the bloodstream reach target organ, extravasate and start to proliferate and disseminate. CSC, cancer stem cell; CTC, tumor circulating cells; DCC, differentiated cancer cell; CAF, cancer associated fibroblast; TAM, tumor associated macrophage; EC, endothelial cell; PC, pericyte cell.