Figure 3.

Role of the pre-metastatic niche in cancer metastasis. Primary tumor cells produce soluble factors and exosomes (A) to trigger the formation of an immature pre-metastatic niche in the target organ (B). Primary tumor conditions (hypoxia, acidity, and interstitial pressure) promote tumor cell migration into the blood vessels. Tumor-secreted factors and exosomes mobilize bone marrow-derived cells (such as CD11b+ myeloid cells) and suppressive immune cells (such as MDSCs, T_reg, and TAMs) to target organs (C). Interactions with local stroma, hypoxia and active ECM remodeling may create a niche with suitable microenvironment conditions for tumor cell colonization (D). Surgery, inflammation, and immunosuppression may increase the number and survival of circulating tumor cells and favor the development of metastasis.