Keratinocyte growth factor-transfection-stimulated adhesion of colorectal cancer cells to extracellular matrices.
The keratinocyte growth factor (KGF) regulates cell growth and behavior in an autocrine or paracrine manner. In colorectal cancer tissues, KGF is expressed in tumor cells and adjacent stromal fibroblasts. We have constructed a KGF-gene-transfected cell line (HCT15-KGF) from a colorectal cancer cell line, HCT-15, that expresses the KGF receptor, and studied the effects of KGF on cell behavior, particularly growth and adhesion to extracellular matrices (ECMs). The amount of KGF secreted from HCT15-KGF was significantly higher than that from a mock-transfected cell line (HCT15-MOCK). The modes of growth of these cell lines were similar. The degree of adhesion of HCT15-KGF to ECMs, including type-IV collagen and fibronectin was higher than that of HCT15-MOCK. The expressions of integrins in both cell lines were not significantly different. However, extracellular-regulated kinase-1 and -2 (ERK1/2) phosphorylation and focal adhesion kinase (FAK) expression that regulate the adhesive functions of integrin families were enhanced in HCT15-KGF. U0126, an inhibitor of the ERK upstream regulator MEK, attenuated the adhesion and spreading of HCT15-KGF cells to type-IV collagen. These results indicate that KGF enhances the adhesion of colorectal cancer cells to type-IV collagen through ERK and FAK signaling pathways.
Kudo
Mitsuhiro
M
Department of Integrative Oncological Pathology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. kudoh@nms.ac.jp
Ishiwata
Toshiyuki
T
Nakazawa
Nando
N
Kawahara
Kiyoko
K
Fujii
Takenori
T
Teduka
Kiyoshi
K
Naito
Zenya
Z
D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D024141:Collagen Type IV / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051523:Fibroblast Growth Factor 7 / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
D024141:Collagen Type IV; D005353:Fibronectins; D016023:Integrins; D017468:Receptors, Fibroblast Growth Factor; D051523:Fibroblast Growth Factor 7; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases