Role of emmprin in endometrial cancer.
BACKGROUND
Extracellular matrix metalloproteinase inducer (Emmprin/CD147) is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer.


METHODS
Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. In addition, the biological functions and inhibitory effects of an emmprin knockdown were investigated in HEC-50B and KLE endometrial cancer cell lines.


RESULTS
The levels of emmprin expression were significantly increased in the endometrial cancer specimens compared with the normal endometrium and endometrial hyperplasia specimens (p < 0.05). The disease-free survival (DFS) and overall survival (OS) rates of patients with high emmprin expression were significantly higher than those of patients with low emmprin expression (DFS: p < 0.001; OS: p < 0.001). Emmprin knockdown by the siRNA led to cell proliferation, migration and invasion through TGF-β, EGF, NF-κB, VEGF, MMP-2, and MMP-9 expression, which in turn resulted in increased levels of E-cadherin and reduced levels of Vimentin and Snail in endometrial cancer.


CONCLUSIONS
The present findings suggest that low emmprin expression might be a predictor of favorable prognosis in endometrial cancer patients, and that emmprin may represent a potential therapeutic target for endometrial cancer.
Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. k-nakamu@cc.okayama-u.ac.jp
Keiichiro
K
Nakamura
Junichi
J
Kodama
Atsushi
A
Hongo
Yuji
Y
Hiramatsu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051926:Basigin / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D051926:Basigin