Table 1 Differences between CAFs at primary tumor sites and MAFs

Origins

• The sources of MAFs and CAFs at primary tumor sites vary according to the organ they locate at instead of the tumor type.

• MAFs may originate from stromal cells from the primary tumor.

Generation

• MAFs can be generated before the arrival of metastatic tumor cells.

• MAFs can be activated not only by adjacent tumor cells and other cells in the metastatic tumor microenvironment, but also by tumor cells and stromal cells at primary sites via extracellular vesicles.

Functions

• MAFs have stronger abilities of promoting tumor cells’ proliferation, migration, invasion and resistance to cytotoxic therapy.

• MAFs decrease CD4⁺ T cell proliferation and suppress T cell activation more strongly.

• MAFs are more highly activated in terms of extracellular matrix remodeling and stiffening ability and proangiogenesis ability.

• S100A4⁺ CAFs inhibit tumor growth and angiogenesis at metastatic sites and not at primary tumor sites.

• Since locations are different, the roles in the process of metastasis are different; for example, MAFs constitute an important part of premetastatic niche and create a friendly environment for metastatic tumor cells.