CCN2 and neoplasm: In mouse models, deficient TGF-β signaling can stimulate tumor cells and stromal cells to produce high levels of TGF-β and other tumor-promoting factors such as CTGF, VEGF, IL-1β, C-X-C motif chemokine ligand (CXCL8), CXCL12, cyclooxygenase(COX)-2, MMPs, collagen, and tenascin C (TNC) which can strongly promote tumor angiogenesis, fibroblasts activation, immune infiltration, and ECM remodeling.760–764,774,843,850