FN1 and cancer: TGF + EVS promoted macrophage chemotaxis without causing a major M1/M2 shift, converting primary human macrophages to a pro-angiogenic phenotype marked by elevated pro-angiogenic factors.121 EV-packaged TGFβ1 can reprogram normal fibroblasts into CAFs in vitro and in vivo by activating the TGFβ-Smad signal pathway and promoting cancer development.122 According to one study, TGF-1 in EV started NFs by controlling fibronectin instead of altering the traditional TGF-Smad signal pathway.