Increased EMMPRIN (CD 147) expression during oral carcinogenesis

Vigneswaran, Nadarajah; Beckers, Simone; Waigel, Sabine; Mensah, John K.; Wu, Jean; Mo, Juan; Fleisher, Kenneth E.; Bouquot, Jerry E.; Sacks, Peter G.; Zacharias, Wolfgang

doi:10.1016/j.yexmp.2005.09.011

Cited by 76 publications

(69 citation statements)

References 45 publications

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“…The fact that CD147 is overexpressed in a number of carcinoma tissues, coupled with its ability to stimulate MMP secretion, suggests that it serves as a key regulator of oncogenesis (Iacono et al, 2007). Indeed, the role of CD147 in carcinogenesis has been reported in gene expression profiling analyses of oral premalignant cells and normal oral epithelial cells (Vigneswaran et al, 2006). We detected HAb18G/CD147 expression in certain atypical hyperplastic hepatocytes in fibrotic livers of mice and found that HAb18G/CD147 was coexpressed with the mesenchymal marker a-smoothmuscle actin (data not shown), suggesting the involvement of CD147-mediated EMT in hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

HAb18G/CD147 promotes epithelial–mesenchymal transition through TGF-β signaling and is transcriptionally regulated by Slug

et al. 2011

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Epithelial-mesenchymal transition (EMT) induced by transforming growth factor-b (TGF-b) is implicated in hepatocarcinogenesis and hepatocellular carcinoma (HCC) metastasis. HAb18G/CD147, which belongs to the CD147 family, is an HCC-associated antigen that has a crucial role in tumor invasion and metastasis. The goal of this study was to investigate the role of HAb18G/ CD147 during EMT in hepatocarcinogenesis. Human normal hepatic cell lines QZG and L02, primary mouse hepatocytes and nude mouse models were used to determine the role of HAb18G/CD147 in EMT, and the involvement of the TGF-b-driven pathway. A dualluciferase reporter assay and ChIP were used to investigate the transcriptional regulation of the CD147 gene. Samples from patients with liver disease were assessed to determine the relationship between HAb18G/CD147 and typical markers for EMT. Our results show that upregulation of HAb18G/CD147 is induced by TGF-b coupled with downregulation of E-cadherin and upregulation of N-cadherin and vimentin. The expression of HAb18G/CD147 is controlled by the cell survival PI3K/ Akt/GSK3b signaling pathway, and is directly regulated by the transcription factor Slug. Transfection of CD147 also induces an elevated expression of TGF-b. CD147-transfected hepatocytes have mesenchymal phenotypes that accelerate tumor formation and tumor metastasis in vivo. Immunohistochemistry analysis shows a negative correlation between HAb18G/CD147 and E-cadherin expression (r s ¼ À0.3622, P ¼ 0.0105), and a positive correlation between HAb18G/CD147 and Slug expression (r s ¼ 0.3064, P ¼ 0.0323) in human HCC tissues. Our study uncovers a novel role of HAb18G/CD147 in mediating EMT in the process of HCC progression and showed that CD147 is a Slug target gene in the signaling cascade TGF-b-PI3K/Akt-GSK3b-Snail-Slug-CD147. Our results suggest that CD147 may be a potential target for the treatment and prevention of HCC.

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Section: Discussionmentioning

confidence: 99%

HAb18G/CD147 promotes epithelial–mesenchymal transition through TGF-β signaling and is transcriptionally regulated by Slug

et al. 2011

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“…Three gastric cell lines exhibited strong EMMPRIN expression according to immunostaining data (Figure 3). Extracellular MMP inducer exists in tumour and transformed cell lines as HG form migrating at B45 -65 kDa and as a less glycosylated (LG) form migrating at B32 -44 kDa, depending on the glycosylation of the core protein (27 kDa) (Riethdorf et al, 2006;Vigneswaran et al, 2006). Western blot also indicated these cell lines strongly expressed EMMPRIN, but the HG form in all cell lines and LG one strongly in HGC-27 and MKN45 and weakly in MKN28 (Figure 4).…”

Section: Extracellular Mmp Inducer Expression In Gastric Carcinomasmentioning

confidence: 94%

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis

et al. 2006

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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 ¼ 234) and non-cancerous mucosa adjacent to carcinoma (n ¼ 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 (Po0.05). 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 (Po0.05), but not with lymph node metastasis, UICC staging or differentiation (P40.05). Interestingly, there was a significantly positive relationship between EMMPRIN expression and MVD in gastric carcinomas (Po0.05). Survival analysis indicated EMMPRIN expression to be negatively linked to favourable prognosis (Po0.05), but not be independent factor for prognosis (P40.05). 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.

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“…Since MCT surface expression is linked to CD147 due to the requirement for interaction between the two proteins for successful cell surface expression (Kirk et al 2000), a coordinate upregulation of CD147 is observed on tumor cells. Indeed, screening of numerous clinical tumor specimens consistently reveals a link between the most aggressive tumors and the highest expression levels of CD147 Rosenthal et al 2003;Ishibashi et al 2004;Reimers et al 2004;Cheng et al 2006;Nabeshima et al 2006;Riethdorf et al 2006;Vigneswaran et al 2006;Zhang et al 2006;Zheng et al 2006). Increased expression of CD147 results in induction of increased MMP production by peritumoral fibrobasts resulting in degradation of the extracellular matrix and a favorable environment for tumor metastasis ( Figure 1B).…”

Section: Hypoxic Induction Of Mct and Cd147 Expression Promotes Tumormentioning

confidence: 95%

CD147 immunoglobulin superfamily receptor function and role in pathology

Iacono

Brown

Greene

et al. 2007

Experimental and Molecular Pathology

232

198

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The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer's disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to up-regulation of CD147 expression and tumor progression is introduced.

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Increased EMMPRIN (CD 147) expression during oral carcinogenesis

Cited by 76 publications

References 45 publications

HAb18G/CD147 promotes epithelial–mesenchymal transition through TGF-β signaling and is transcriptionally regulated by Slug

HAb18G/CD147 promotes epithelial–mesenchymal transition through TGF-β signaling and is transcriptionally regulated by Slug

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis

CD147 immunoglobulin superfamily receptor function and role in pathology

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