CHARACTERIZATION OF KERATINOCYTE GROWTH-FACTOR AND RECEPTOR EXPRESSION IN HUMAN PANCREATIC-CANCER

Keratinocyte growth factor (KGF) is an angiogenic and mitogenic polype ptide that has been implicated in cancer growth and tissue development and repair. Its actions are dependent on its binding to a specific ce ll-surface KGF receptor (KGFR), which is encoded by the fibroblast gro wth factor (FGF) receptor type LI (FGFR-2) gene. In the present study, we compared the immunohistochemical localization of KGF and KGFR/FGFR -2 in the normal and cancerous pancreas using specific antibodies that recognize KGF and KGFR/FGFR-2 and examined the expression of KGF, KGF R, and FGFR-2 in human pancreatic cancer by in situ hybridization with the corresponding riboprobes, In the normal pancreas, KGF immunoreact ivity was present principally in the islet cells, whereas KGFR/FGFR-2 immunoreactivity was present both in the islet and ductal cells. In th e pancreatic cancers, moderate KGF and moderate to strong KGFR/FGFR-2 immunoreactivity was present in many of the cancer cells. Furthermore, the ductal and acinar cells adjacent to the cancer cells exhibited mo derate to strong KGF and KGFR/FGFR-2 immunoreactivity. By in situ hybr idization, KGF, KGFR, and FGFR-2 were overexpressed and co-localized i n the cancer cells within the pancreatic tumor mass but were even more abundant in the acinar and ductal cells adjacent to the cancer cells. These findings indicate that KGF, KGFR, and FGFR-2 are overexpressed in both the cancer cells and the adjacent pancreatic parenchyma and ra ise the possibility that KGF may act in an autocrine and paracrine man ner to enhance pancreatic cancer cell growth in vivo.