Increased EMMPRIN (CD 147) expression during oral carcinogenesis.
Gene expression profiling of oral premalignant (OPM) cells and normal oral epithelial (NOR) cells showed that EMMPRIN expression was markedly upregulated in OPM cells compared to NOR cells. We used an oral squamous cell carcinoma (OSCC) progression model composed of cell lines, organotypic cultures and tissue specimens to characterize EMMPRIN expression patterns by microarray analysis, qRT-PCR, Western blotting and immunohistochemistry. EMMPRIN levels are elevated in OPM and primary and metastatic OSCC cells as compared to NOR. EMMPRIN was detected as high and low glycosylated forms in the OPM and OSCC cellular extracts and was released in the media by OSCC cells but not by OPM cells. EMMPRIN expression in an organotypic culture model of normal and OPM mucosae mirrored the expression patterns in the respective tissues in vivo. EMMPRIN expression was limited to basal cells of normal, benign hyperkeratotic and inflammatory (lichen planus) oral mucosa. EMMPRIN expression is increased in dysplastic leukoplakias spreading to more superficial layers, and its expression levels correlated significantly with the degree of dysplasia. Primary and metastatic OSCC showed strong cell surface expression of EMMPRIN. These results suggest that EMMPRIN overexpression occurs at a very early stage of oral carcinogenesis and plays a contributing role in OSCC tumorigenesis.
Vigneswaran
Nadarajah
N
Department of Diagnostic Sciences, The University of Texas Health Science Center at Houston, Dental Branch, 6516 M.D. Anderson Blvd., Room 3.094G, Houston, TX 77030, USA. Nadarajah.Vigneswaran@UTH.TMC.EDU
Beckers
Simone
S
Waigel
Sabine
S
Mensah
John
J
Wu
Jean
J
Mo
Juan
J
Fleisher
Kenneth E
KE
Bouquot
Jerry
J
Sacks
Peter G
PG
Zacharias
Wolfgang
W
D000368:Aged; D051926:Basigin / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D007972:Leukoplakia, Oral / Q000473:pathology; D046228:Microarray Analysis; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*
D012333:RNA, Messenger; D051926:Basigin