Expression of keratinocyte growth factor and its receptor in colorectal cancer.
OBJECTIVE
The mesenchymal derived keratinocyte growth factor stimulates growth, differentiation and migration of intestinal epithelial cells. In the human gastrointestinal tract an overexpression of this growth factor has been reported in inflammatory bowel disease and pancreatic cancer. In the present study we investigated expression patterns of keratinocyte growth factor and receptor in normal and neoplastic colonic mucosa and in metastases. Furthermore, biological effects on normal intestinal and colorectal cancer cell lines were determined.


METHODS
Expression patterns were analysed at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by Western blotting. Localization of ligand and receptor in normal intestinal mucosa and cancer tissue was investigated by immunohistochemistry. Mitogenic effects of keratinocyte growth factor were assayed by [3H]thymidine incorporation in normal (Intestine-407, IEC-6, IEC-18) and colorectal cancer cell lines (Colo320, LoVo, SW403, SW707).


RESULTS
mRNA expression of keratinocyte growth factor and receptor was detected in the majority of normal and cancer samples without significant alterations. At the protein level keratinocyte growth factor expression did not differ between normal and malignant specimens, whereas protein expression of the receptor was increased up to twofold in well- to moderately differentiated colorectal cancers. DNA synthesis was significantly stimulated by keratinocyte growth factor in all three normal intestinal cell lines, whereas this growth factor did not significantly alter the [3H]thymidine incorporation in the colorectal cancer cell lines.


CONCLUSIONS
Keratinocyte growth factor and its receptor were detected in the majority of samples from normal and neoplastic colonic mucosa, with an overexpression 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.
Otte
J M
JM
Christian-Albrechts-Universität, Kiel, Germany; Karol Marcinowski University, Poznan, Poland.
Schmitz
F
F
Banasiewicz
T
T
Drews
M
M
Fölsch
U R
UR
Herzig
K H
KH
D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D017978:Receptors, Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors