MAF (Metastasis-Associated Fibroblast)

Metastasis-associated fibroblasts are activated fibroblasts residing at a metastatic site, the counterpart of cancer-associated fibroblasts in the primary tumor. Despite arising from different sources and organs, MAFs and CAFs appear to support the same processes: cancer cell proliferation, invasion, angiogenesis, immunosuppression and drug resistance. Myofibroblastic, inflammatory and mesothelial MAF subtypes have been described in liver metastases of colorectal and pancreatic tumors.

Their reported origins are varied - resident mesenchymal cells, pericytes, hepatic stellate cells, mesothelial cells, bone-marrow-derived mesenchymal stem cells, and CAFs that travel from the primary tumor, which is how MAFs come to be present even in tissues such as brain that lack resident fibroblasts. They are activated by the same TGF-beta, PDGFR-alpha and IL-1alpha/beta signaling as CAFs, and extracellular vesicles can precondition a secondary site by converting resident cells into MAFs before colonization.

Functionally, MAFs deposit and remodel matrix, restrain CD4+ and CD8+ T cell proliferation through CCL2 and CXCL12, support cancer cell growth through PDGF, hyaluronic acid and HGF, and help maintain cancer cell stemness by producing periostin to augment WNT signaling. Compared with CAFs in primary tumors they remain little studied, and whether CAFs give rise to MAFs has not been settled by lineage tracing.