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 endo thelial cells, In the present study hCTGF was isolated as immediate early t arget 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/TG F 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 pancreati c cancer tissues were shown to overexpress high levels of CTGF transcripts. CTGF transcript levels in pancreatic cancer tissues and nude mouse xenogra ft tumors showed a good correlation to the degree of fibrosis, III situ hyb ridization and the nude mouse experiments revealed that in pancreatic cance r tissues, fibroblasts are the predominant site of CTGF transcription, wher eas the tumor cells appear to contribute to a lesser extent. We conclude th at CTGF may be of paramount importance for the development of the character istic desmoplastic reaction in pancreatic cancer tissues.