Figure 2.

Tumor—macrophage—CTC interactions and mediators. Monocytes are recruited from the circulation and differentiate to protumor macrophages (TAMs). Tumor/CTC and macrophage interactions result in release of sever cytokines/chemokines and proteases, including CHI3L1. Eventually CTCs are generated which express CHI3L1, VEGF and MMP9 which enables them to intravasate. A subpopulation of the heterogenous CTCs form tumorospheres (scanning electron microscopy of a BHGc26 tumorosphere inserted), survive in the circulation and extravasate to form secondary lesions in distal organs, including bone, liver and brain. CTC, circulating tumor cells.