Overexpression of keratinocyte growth factor in cancer cells and enterochromaffin cells in human colorectal cancer

Keratinocyte growth factor (KGF) is a mitogenic polypeptide that is mainly synthesized by mesenchymal cells. Its actions are dependent on its binding to a specific cell-surface KGF receptor (KGFR), which is localized in epith elial cells. In the present study, the expression level of KGF and KGFR mes senger RNA (mRNA), and the localization of these mRNA and proteins in tumor specimens obtained from 12 human colorectal cancer cases were estimated. C ompetitive reverse transcriptase-polymerase chain reaction (RT-PCR) reveale d the expression of KGF and KGFR mRNA in both colorectal cancer and normal colorectal tissues. In specimens from 10 of the 12 cancer cases, the KGF mR NA level was higher in the specimens obtained from the cancerous portions t han in those obtained from non-cancerous tissues of the same cases. KGFR mR NA was higher in cancerous tissues in eight of 12 cases. To localize the KG F protein in normal and cancerous human colorectal tissues, immunohistochem istry was employed. In normal colorectal tissue, faint KGF immunoreactivity was present in a few fibroblasts. In contrast, strong KGF immunoreactivity was present in many of the neuroendocrine cells present in close proximity to cancer cells, and moderate immunoreactivity was recognized in the cance r cells themselves and adjacent fibroblasts. KGF-positive neuroendocrine ce lls also showed serotonin immunoreactivity, indicating that they were enter ochromaffin cells. By in situ hybridization, both KGF and KGFR mRNA were co -overexpressed in these colorectal cancer cells, and KGF mRNA was recognize d in neuroendocrine cells lying in close proximity to the cancer cells. The se findings indicate the possibility that KGF acts in both a paracrine and autocrine manner to induce colorectal cancer cell growth in vivo.