In vitro studies indicate that SDF-1 expression induces a number of pro-tumorigenic responses, such as Bcl-2, and activates the PI3K/Akt pathway, promoting increased CCA cell invasion, prolonged survival, and epithelial-to-mesenchymal transition [97]. Another study using 2D co-culture systems showed that the contact of α-Smooth Muscle-Actin-positive (α-SMA) myofibroblastic CAFs and iCCA cells increased tumor cell proliferation and switched cells into the active stages of the cell cycle [98]. Here, CXCL12 is linked to cholangiocarcinoma.