Figure 1.

Comparison between normal thyroid fibroblasts and thyroid CAFs. Normal thyroid fibroblasts and thyroid CAFs display molecular and functional differences. Normal thyroid fibroblasts are quiescent cells, characterized by no expression of FAPα, Tn-C and α-SMA markers, which are instead highly expressed by thyroid CAFs. Fibroblast activation and CAF differentiation are associated with CAF metabolic reprogramming towards a more glycolytic phenotype, as demonstrated by the increased expression of GLUT1 and LDH-A. Conversely, normal thyroid fibroblasts prefer oxidative phosphorylation (OXPHOS) for energy supply. Furthermore, thyroid CAFs and their normal counterpart exhibit differences in their migratory capability, proliferation rate and synthetic and secretory profiles. In particular, thyroid CAFs proliferate and migrate faster than normal thyroid fibroblasts and further increase their capability to produce and remodel the ECM, produce inflammatory proteins and modulate immune cells. All of these changes lead thyroid CAFs to acquire a pro-tumorigenic phenotype.