Transforming growth factor-beta 1 induces desmoplasia in an experimental model of human pancreatic carcinoma

Proliferation of fibrotic tissue (desmoplasia) is one of the hallmarks of s everal epithelial tumors including pancreatic adenocarcinoma, This tissue r eaction may be deleterious or advantageous to the host or tumor. In a syste matic analysis, we identified two growth factors expressed by human pancrea tic carcinoma cells that are positively correlated with the ability to indu ce fibroblast proliferation both ill vitro and ill vivo, i.e., transforming growth factor (TGF)-beta1 and fibroblast growth factor-2, Here we demonstr ate that the overexpression of TGF-beta1 induced upregulation of matrix pro teins and growth factors in the TGF beta1-transfected pancreatic tumor cell s. Furthermore, transfection of PANC-1 cells induces the same change in fib roblasts in either cocultivation experiments or when they are grown in cond itioned medium from TGF-beta1-transfected PANC-1 cells. TGF-beta1-transfect ed pancreatic tumor cells induced a rich stroma after orthotopical transpla ntation in the nude mouse pancreas. The transfer of a single growth factor, TGF-beta1, conveys the ability to induce a fibroblast response similar to that seen in desmoplasia in human pancreatic adenocarcinoma, This effect ca nnot only be attributed to direct effects of TGF-beta1 but also results fro m the up-regulation of several other factors including collagen type I, con nective tissue growth factor, and platelet-derived growth factor.