Figure 2.

Pro-metastatic effects exerted by CAFs within heterotypic CTC clusters and at the secondary site. In circulation, CAFs enhance the metastatic potential of CTCs by conferring to them shear stress resistance through the establishment of strong cellular adhesions. Moreover, CAFs protect CTCs from apoptosis by activating cell survival pathways and maintaining CTC proliferation. At the metastatic site, CAF-secreted factors and tumor-derived exosomes create an appropriate environment for CTC growth, also supported by CAF-mediated immunosuppression. Additionally, circulating CAFs can be recruited to secondary sites and contribute to the establishment of the metastatic niche.