M. Watanabe et al., Overexpression of keratinocyte growth factor in cancer cells and enterochromaffin cells in human colorectal cancer, PATHOL INT, 50(5), 2000, pp. 363-372
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.