Expression of keratinocyte growth factor and its receptor in colorectal cancer

Background and aims The mesenchymal derived keratinocyte growth factor stim ulates growth, differentiation and migration of intestinal epithelial cells , In the human gastrointestinal tract an overexpression of this growth fact or has been reported in inflammatory bowel disease and pancreatic cancer. I n the present study we investigated expression patterns of keratinocyte gro wth factor and receptor in normal and neoplastic colonic mucosa and in meta stases. Furthermore, biological effects on normal intestinal and colorectal cancer cell lines were determined. Materials and methods Expression patterns were analysed at the mRNA level b y reverse transcription-polymerase chain. reaction (RT-PCR) and at the prot ein level by Western blotting Localization of ligand and receptor in normal intestinal mucosa and cancer tissue was investigated by immunohistochemist ry. Mitogenic effects of keratinocyte growth factor were assayed by [H-3]th ymidine incorporation in normal (Intestine-407, IEC-6, IEC-18) and colorect al cancer cell lines (Colo320, LoVo, SW403, SW707). Results mRNA expression of keratinocyte growth factor and receptor was dete cted in the majority of normal and cancer samples without significant alter ations. At the protein level keratinocyte growth factor expression did not differ between normal and malignant specimens, whereas protein expression o f the receptor was increased up to twofold in well- to moderately different iated colorectal cancers. DNA synthesis was significantly stimulated by ker atinocyte growth factor in all three normal intestinal cell lines, whereas this growth factor did not significantly alter the [H-3]thymidine incorpora tion in the colorectal cancer cell lines. Conclusion keratinocyte growth factor and its receptor were detected in the majority of samples from normal and neoplastic colonic mucose, with an ove rexpression of the receptor seen in the more differentiated tumour samples. Keratinocyte growth factor is a strong mitogen for normal intestinal cells , whereas it is less effective in neoplastic cells.