FIBROBLAST GROWTH FACTOR-5 STIMULATES MITOGENIC SIGNALING AND IS OVEREXPRESSED IN HUMAN PANCREATIC-CANCER - EVIDENCE FOR AUTOCRINE AND PARACRINE ACTIONS

Fibroblast growth factor (FGF)-1 and -2 are overexpressed in human pan creatic cancer. In this study the role of FGF-5 in human pancreatic ca ncer was investigated, as FGF-5 has a classical signal sequence for se cretion not found in FGF-1 or -2. Northern blot analysis with a 306 bp FGF-5 cDNA revealed the presence of 4.0 kb and 1.6 kb FGF-5 mRNA tran scripts in both normal and cancerous pancreatic tissues. Densitometric analysis indicated that 4.0 kb and 1.6 kb FGF-5 mRNA transcripts leve ls were increased 2.4- and 2.7-fold in the cancers by comparison with normal tissues, respectively (P<0.002, P<0.0001). Immunohistochemistry and in situ hybridization demonstrated that FGF-5 localized in the ca ncer cells, stromal fibroblast and inflitrating macrophages. FGF-5 mRN A was also detected in COLO-357 human pancreatic cancer cells. Further more, secreted FGF-5 protein was present in conditioned medium of COLO -357 cells. Exogeneous FGF-5 (0.37 nM) increased the growth of COLO-35 7 cells by 48% (P<0.0001) and increased mitogen-activated protein kina se activity. COLO-357 cells expressed the IIIc isoform of the type I F GF receptor, the preferred FGF receptor for FGF-5. These observations suggest that FGF-5 may participate in autocrine and paracrine pathways promoting pancreatic cancer cell growth in vivo.