Fig. 3

EMT in the metastatic cascade. Distinct stromal cells promote the dissemination of carcinoma cells, such as myofibroblasts, natural killer cells, T or B lymphocytes and macrophages. The scheme outlines the transition from an epithelial-like phenotype to a mesenchymal-like phenotype during local invasion and intravasation. Carcinoma cells can re-acquire through MET an epithelial-like phenotype following extravasation colonization of the secondary sites and proliferation. Macrophages can initiate a feedback-loop of EGF and Colony Stimulating Factor 1 (CSF1) to promote EMT. Myofibroblasts produce and reprogram ECM, secrete pro-inflammatory factors, and induce epithelial cell proliferation and invasion. BMDC contribute to the genesis of the premetastatic niche. Lymphocyte trafficking is also an important metastasis regulator. MDSCs interact with innate/adaptive immune cells, and promote cancer escape and angiogenesis in the cancer niche. MDSC and NK cells are also critical for MET process by populate premetastatic niches, where they regulate metastatic dissemination, initiate and promote tumor colonization