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. Author manuscript; available in PMC: 2020 Aug 1.
Published in final edited form as: Biochim Biophys Acta Rev Cancer. 2019 Jun 14;1872(1):89–102. doi: 10.1016/j.bbcan.2019.06.002

Figure 1. Mechanism of metastatic progression.

Figure 1.

During primary tumor growth cancer cells can shed into the circulation and disseminate to distant sites, which may even occur at a very early stage of primary tumor development. Tumor-secreted factors can recruit, expand and activate various stromal cells, including spleen- and bone marrow-resident cells, and facilitate the formation of pre-metastatic niches at secondary sites. The recruited stromal cells aid the dissemination of carcinoma cells survival in circulation, and metastatic seeding and colonization. Immune evasion and angiogenesis are necessary steps of tumor progression mediated by tumor- and stroma-derived factors. Self-seeding of the tumor at later stages and re-seeding from metastatic lesions increase intratumoral heterogeneity and the risk of therapeutic resistance.