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 epithelial cells. In the present study, the expression level of KGF and KGFR messenger RNA (mRNA), and the localization of these mRNA and proteins in tumor specimens obtained from 12 human colorectal cancer cases were estimated. Competitive reverse transcriptase-polymerase chain reaction (RT-PCR) revealed 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 mRNA level was higher in the specimens obtained from the cancerous portions than in those obtained from non-cancerous tissues of the same cases. KGFR mRNA was higher in cancerous tissues in eight of 12 cases. To localize the KGF protein in normal and cancerous human colorectal tissues, immunohistochemistry 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 cancer cells themselves and adjacent fibroblasts. KGF-positive neuroendocrine cells also showed serotonin immunoreactivity, indicating that they were enterochromaffin cells. By in situ hybridization, both KGF and KGFR mRNA were co-overexpressed in these colorectal cancer cells, and KGF mRNA was recognized in neuroendocrine cells lying in close proximity to the cancer cells. These findings indicate the possibility that KGF acts in both a paracrine and autocrine manner to induce colorectal cancer cell growth in vivo.