FIGURE 2.

Cancer cells undergo EMT and invade into circulation. (A) A single transformed epithelial cell remains quiescent for a period of time. (B, C). The transformed cells proliferate and generate a small intraepithelial colony, accompanied by the formation of cancer stem cells. Cancer cells destroy the basement membrane, undergo EMT, and migrate and invade through the basement membrane and extracellular matrix. Normal extracellular matrix undergoes cancer‐associated remodel. Meanwhile, cells and molecular components in tumor microenvironment (TME; CAFs, TAMs, neutrophils, MSCs…) surrounding the primary tumor enhance cancer cell survival, proliferation and metastasis. (D) Cancer cells escaping from primary tumors can invade into the circulation as single CTCs or multicellular CTC clusters. Abbreviations: BM, basement membrane; CAF, cancer‐associated fibroblast; CTC, circulating tumor cell; EC, endothelial cell; ECM, extracellular matrix; EMT, epithelial‐to‐mesenchymal transition; MSC, mesenchymal stem cell; TAM, tumor‐associated macrophage