Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis.
Tumour growth depends on angiogenesis, which is closely associated with vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Extracellular MMP inducer (EMMPRIN) was reported to involve in the progression of malignancies by regulating expression of VEGF and MMPs in stromal cells. To clarify the role of EMMPRIN in progression and angiogenesis of gastric carcinoma, expression of EMMPRIN, ki-67, MMP-2, MMP-9 and VEGF was examined on tissue microarray containing gastric carcinomas (n=234) and non-cancerous mucosa adjacent to carcinoma (n=85) by immunohistochemistry. Additionally, microvessel density (MVD) was assessed after labelling with anti-CD34 antibody. Extracellular MMP inducer expression was compared with clinicopathological parameters of tumours, including levels of ki-67, MMP-2, MMP-9 and vascular endothelial growth factor (VEGF), MVD as well as survival time of carcinoma patients. Gastric carcinoma cell lines (HGC-27, MKN28 and MKN45) were studied for EMMPRIN expression by immunohistochemistry and Western blot. Extracellular MMP inducer expression was gradually increased from normal mucosa to carcinomas through hyperplastic or metaplastic mucosa of the stomach (P<0.05). There was strong EMMPRIN expression in all gastric carcinoma cell lines despite different levels of glycosylation. Extracellular MMP inducer expression was positively correlated with tumour size, depth of invasion, lymphatic invasion, expression of ki-67, MMP-2, MMP-9 and VEGF of tumours (P<0.05), but not with lymph node metastasis, UICC staging or differentiation (P>0.05). Interestingly, there was a significantly positive relationship between EMMPRIN expression and MVD in gastric carcinomas (P<0.05). Survival analysis indicated EMMPRIN expression to be negatively linked to favourable prognosis (P<0.05), but not be independent factor for prognosis (P>0.05). Further analysis showed three independent prognostic factors, depth of invasion, lymphatic and venous invasion, to influence the relationship between EMMPRIN expression and prognosis. Upregulated expression of EMMPRIN possibly contributes to genesis, growth and local invasion of gastric carcinomas. Altered EMMPRIN expression might enhance growth, invasion and angiogenesis of gastric carcinoma via upregulating MMP expression of both stromal fibroblasts and gastric cancer cells and could be considered as an objective and effective marker to predict invasion and prognosis.
Zheng
H-C
HC
Department of Diagnostic Pathology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Takahashi
H
H
Murai
Y
Y
Cui
Z-G
ZG
Nomoto
K
K
Miwa
S
S
Tsuneyama
K
K
Takano
Y
Y
D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051926:Basigin / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008833:Microcirculation; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C497886:BSG protein, human; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051926:Basigin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9