Functional expression of HGF and its receptor in human colorectal cancer.
BACKGROUND
Hepatocyte growth factor (HGF) stimulates proliferation, migration and morphogenesis of epithelial cells by specific binding to its receptor c-met. Overexpression of HGF or c-met has been reported for human gastric or pancreatic cancer. In colorectal cancer overexpression of c-met but not HGF has been shown. However, elevated HGF serum levels have been detected in colorectal cancer patients. Therefore, the present study was performed to investigate expression patterns of both c-met and HGF in colorectal cancers and metastasis in comparison to normal mucosa. Furthermore, the mitogenic actions of HGF on colorectal cancer cells were studied in vitro.


METHODS
Expression of c-met and HGF were analyzed by RT-PCR and Western blotting and localized in the tissues utilizing immunohistochemistry. Mitogenic effects of HGF were determined in four human colon cancer cell lines by (3)H-thymidine incorporation studies.


RESULTS
C-met and HGF mRNA were detectable in 60% of the normal specimen, but in the majority of cancer samples, and in just 33% of the liver metastasis. In cancer samples a coexpression of c-met and HGF was detected in 77% of the specimens. The extent of protein expression of receptor and ligand correlated with the mRNA expression. Moreover, c-met protein expression was increased 2- to 3-fold in colorectal cancers. C-met was detected in cells of epithelial origin, whereas HGF was expressed by mesenchymal cells. In vitro, HGF significantly stimulated cell growth in all four cell lines.


CONCLUSIONS
Overexpression of c-met protein in colorectal cancers is combined with an expression of HGF in the majority of cases suggesting a paracrine manner of growth enhancement, while only a weak expression of c-met or HGF was detected in metastatic tissues.
Otte
J M
JM
First Department of Internal Medicine, Christian Albrechts University, Kiel, Germany.
Schmitz
F
F
Kiehne
K
K
Stechele
H U
HU
Banasiewicz
T
T
Krokowicz
P
P
Nakamura
T
T
Fölsch
U R
UR
Herzig
K
K
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met