FIGURE 2.

Origin and function of CAFs. Schematic representations of possible CAF cell origins have been depicted, as evidenced to date. Different types of cellular differentiation, trans-differentiation, and de-differentiations give rise to the generation of CAFs. CAFs show a plethora of activities in accord with and against cancer cell survival and malignancy, evidently in a stage-specific manner. The only event that results in the suppression of tumors occurs when the CAF-derived secretome includes TGFβ inhibitors. The other roles of CAFs in cancer include the induction of all the hallmarks of cancer via the secretion of various cytokines, chemokines, growth factors, carbohydrate intermediates, and nitrogen sources (amino acids). Their activities include induction of cancer stemness, metastasis, migration, invasion, angiogenesis, ECM remodeling, immunomodulation, metabolic manipulation, and therapeutic resistance (Karnoub et al., 2007; Mani et al., 2008; Erez et al., 2010; Baccelli and Trumpp, 2012; Oskarsson et al., 2014; Albrengues et al., 2015; Yeon et al., 2018; Fiori et al., 2019; Sahai et al., 2020a; Shen et al., 2020; Loh and Ma, 2021; Ping et al., 2021; Wu et al., 2021).