1) Through different signaling pathways, including TGF-β, PDGF, IL-1, 6, 8, and etc., transformed tumor cells activate the quiescent stromal cells and initiate the extensive desmoplastic reaction; Microvesicles shed from tumor cells could also convey signals to target stromal cells through those bioactive molecules embedded within them. 2) Once activated, pancreatic stellate cells could perpetuate the desmoplastic reaction through a list of signaling pathways in an autocrine manner. Activated pancreatic stellate cells proliferate, contract, migrate, modulate extracellular matrix, and finally stimulate the growth and migration of tumor cells.