EXPRESSION OF CONNECTIVE-TISSUE GROWTH-FACTOR MESSENGER-RNA IN THE FIBROUS STROMA OF MAMMARY-TUMORS

Desmoplasia, the formation of highly cellular, excessive connective ti ssue stroma associated with some cancers, shares many features with th e wound healing response. Since connective tissue growth factor (CTGF) has previously been demonstrated to play a role in wound repair, we w anted to determine if it might be involved in the pathogenesis of stro mal desmoplasia in mammary cancer. We assayed 11 human invasive mammar y ductal carcinomas by Northern blot and 7 out of 11 were positive for both CTGF expression and transforming growth th factor-beta 1 (TGF-be ta 1, a principal CTGF inducer). One specimen was positive only for TG F-beta 1. The remaining 3 tumors lacked significant stromal involvemen t and were negative for either factor. In every case we assayed, in wh ich there was marked connective tissue involvement, both CTGF and TGF- beta 1 messages were found. We also assayed 3 murine mammary tumor mod els. The GI-101 xenograft model had marked stroma and was positive for both factors in-vivo, but positive for only TGF-beta 1 mRNA expressio n in culture where fibroblasts were absent. The DMBA murine tumor lack ed significant stroma and,vas negative for CTGF and TGF-beta 1 express ion by Northern blot, while the stromal rich DMBA-MMTV tumor contained multifocal desmoplasia and was positive for both factors. We performe d in-situ hybridization for CTGF and TGF-beta 1 on the GI-101 and DMBA -MMTV tumors. CTGF message was observed only in the fibroblasts of the stroma, while TGF-beta 1 mRNA hybridization was present in tumor epit helial cells and leukocytes. These results suggest that cancer stroma formation involves induction of similar fibroproliferative growth fact ors (TGF-beta 1 and CTGF) as wound repair. (C) 1997 Elsevier Science L td. All rights reserved.