Expression and differential regulation of connective tissue growth factor in pancreatic cancer cells

CTGF is an immediate early growth responsive gene that has been shown to be a downstream mediator of TGF beta actions in fibroblasts and vascular endothelial cells, In the present study hCTGF was isolated as immediate early target gene of EGF/TGF alpha in human pancreatic cancer cells by suppression hybridization, CTGF transcripts were found in 13/15 pancreatic cancer cell lines incubated with 10% serum, In 3/7 pancreatic cancer cell lines EGF/TGF alpha induced a significant rise of CTGF transcript levels peaking 1-2 h after the start of treatment. TGF beta increased CTGF transcript levels in 2/7 pancreatic cancer cell lines after 4 h of treatment and this elevation was sustained after 24 h, Only treatment with TGF beta was accompanied by a parallel induction of collagen type I transcription. 15/19 human pancreatic cancer tissues were shown to overexpress high levels of CTGF transcripts. CTGF transcript levels in pancreatic cancer tissues and nude mouse xenograft tumors showed a good correlation to the degree of fibrosis, III situ hybridization and the nude mouse experiments revealed that in pancreatic cancer tissues, fibroblasts are the predominant site of CTGF transcription, whereas the tumor cells appear to contribute to a lesser extent. We conclude that CTGF may be of paramount importance for the development of the characteristic desmoplastic reaction in pancreatic cancer tissues.