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. 2020 Aug 19;11:1289. doi: 10.3389/fphar.2020.01289

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Copyright © 2020 Tian, Jiang, Kim, Guan, Nicolls and Rockson

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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Process of cancer metastasis. 1) Genetic risks and environmental factors (e.g., inflammation) cause epithelial cell transform into cancer cell phenotype. 2) Cancer cells and cancer stem cells proliferate to generate primary tumor. 3) The carcinoma cells recruit a variety of stromal cells and immune cells to form tumor microenvironment (TME). 4) Cancer cells, under the influence of TME, acquire an invasive phenotype through epithelial-to-mesenchymal-transition (EMT) and intravasate into blood vascular or lymphatic circulation. 5) The malignant cancer cells exit the circulation and develop into secondary tumor at the distant organs.