Expression of emmprin (CD147), a cell surface inducer of matrix metalloproteinases, in normal human brain and gliomas

Sameshima, Tetsuro; Nabeshima, Kazuki; Toole, Bryan P.; Yokogami, Kiyotaka; Okada, Yasunori; Goya, Tomokazu; Koono, Masashi; Wakisaka, Shinichiro

doi:10.1002/1097-0215(20001001)88:1<21::aid-ijc4>3.0.co;2-s

Cited by 136 publications

(102 citation statements)

References 38 publications

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“…EMM-PRIN expression also was reported to be significantly elevated in gliomas compared to normal brain tissue. 33 Consistent with our observations, glioblastoma multiforme displayed the highest level of EMMPRIN expression. Expression of EMMPRIN antisense RNA has been shown to result in decreased migration and invasion of glioblastoma cells.…”

Section: Discussionsupporting

confidence: 88%

High incidence of EMMPRIN expression in human tumors

Riethdorf

Reimers

Assmann

et al. 2006

Intl Journal of Cancer

205

172

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Extracellular matrix metalloproteinase inducer expressed by tumor cells stimulates peritumoral fibroblasts to produce matrix metalloproteinases, thus contributing to tumor invasion and metastasis. To assess its suitability as potential therapeutic target, the overall incidence of EMMPRIN expression in normal and neoplastic tissues was analyzed. EMMPRIN expression was detected immunohistochemically using monoclonal antibodies MEM-M6/1 and HIM6 and tissue microarrays with 2,348 and 608 tissue samples from 129 distinct tumor types and 76 different normal tissues, respectively. Expression and glycosylation state of EMMPRIN in human breast cancer cells were analyzed by Western blot analysis with monoclonal antibodies recognizing distinct carbohydrate structures and biochemical methods. EMMPRIN expression was found in 112 of 129 tumor entities analyzed with malignant tumors being EMMPRIN positive more frequently than benign tumors. A remarkable heterogeneity in EMMPRIN expression between tumor entities was observed. Among others, squamous-cell carcinomas (60-100%), pancreatic (87%), chromophobic kidney (83%), hepatocellular (83%) or medullary breast (83%) adenocarcinomas as well as glioblastoma multiforme (79%) presented with a particular high incidence of EMMPRIN expression. There were a limited number of EMMPRIN-positive normal cell types including proliferatively active and differentiating epithelial cells, germ cells, myocardial cells in the left heart ventricle or vascular endothelial cells of the brain. We could further demonstrate that breast cancer cells expressed EMMPRIN isoforms differing in the presence or absence of Lewis X glycan structures. Our results may assist in defining the suitability of EMMPRIN as therapeutic target and predicting negative side effects. ' 2006 Wiley-Liss, Inc.Key words: extracellular matrix metalloproteinase inducer expression; human normal tissues; human tumors; glycosylation Tumor cell invasion and metastasis requires degradation of extracellular matrix components, which is mainly achieved by various proteolytic enzymes including zinc-dependent matrix metalloproteinases (MMPs). Analysis of MMP expression patterns in tumor specimens revealed that the majority of these enzymes are produced by stromal cells surrounding the tumor rather than by tumor cells themselves. An increasing body of evidence, however, suggests that MMP synthesis is stimulated by tumor cells in a paracrine fashion. This stimulation is at least partially attributed to extracellular matrix metalloproteinase inducer (EMMPRIN, also designated CD147 or basigin), a 58 kDa surface glycoprotein of the immunoglobulin superfamily, originally purified from the plasma membrane of cancer cells. 1 EMMPRIN has been demonstrated to stimulate production of MMP-1, -2, -3, -9, -14, -15 in fibroblasts surrounding tumor cells. 2 As shown by Sun and Hemler, 3 EMMPRIN also appears to participate in the induction of MMP production in tumor cells in an autocrine fashion. Accordingly, MDA-MB-436 human breast cancer cells recombinantly...

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Section: Discussionsupporting

confidence: 88%

High incidence of EMMPRIN expression in human tumors

Riethdorf

Reimers

Assmann

et al. 2006

Intl Journal of Cancer

205

172

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“…6 Previous studies have shown that CD147 is highly expressed in melanoma and glioma cells, and induces tumor invasion by stimulating generation of MMPs by adjacent fibroblast cells or other stromal cells. 14,15 Although normal cells also express CD147, it seems that CD147 is highly expressed in many human cancer cells, 26 -30 and the tumor-specific induction of MMPs in facilitating tumor invasion and metastasis caused by CD147 may be due to different glycosylation or modification of CD147 molecules in tumor cells as compared with the normal cells. 6 Transfection of CD147 cDNA into slow-growing breast cancer cells in vivo turned them into more tumorigenic and invasive cancer cells as compared with the mock transfected cells.…”

Section: Discussionmentioning

confidence: 99%

“…6,[11][12][13] Studies have shown that CypA binds to CD147 and transmits a signal to downstream cascades. CD147 is found to be highly expressed in human gliomas as compared with nonneoplastic brain tissues, 14 and is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases (MMPs) by adjacent fibroblasts, resulting in tumor invasion and metastasis. 15 However, the roles of CD147 in pancreatic cancer growth are not clear.…”

mentioning

confidence: 99%

Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147

Li¹,

Zhai

Bharadwaj³

et al. 2006

Cancer

140

127

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BACKGROUNDAlthough overexpression of cyclophilin A (CypA) is associated with several types of cancer, its role in pancreatic cancer has not been studied. In this study the expression of CypA and its receptor CD147 on pancreatic cancer was determined as well as the effect of exogenous CypA on pancreatic cancer cell proliferation.METHODSThe expression of CypA and CD147 in human pancreatic cancer cell lines and tissues was determined with real‐time reverse transcriptase polymerase chain reaction (RT‐PCR), Western blot, and immunostaining. Cell proliferation in response to CypA was performed by [3H]thymidine incorporation assay. Phosphorylation of MAPK and cytokine secretion profiles in pancreatic cancer cells were determined by using the Bio‐Plex phosphoprotein assay and cytokine assay.RESULTSPancreatic cancer cell lines expressed significantly higher levels of CypA and CD147 than normal human pancreatic ductal epithelium (HPDE) cells. Expression of CypA and CD147 was also substantially higher in human pancreatic adenocarcinoma tissues than those in normal pancreatic tissues. Addition of exogenous CypA significantly stimulated pancreatic cancer cell proliferation in a dose‐dependent manner and this effect was effectively blocked by pretreatment with anti‐CD147 antibody. In addition, CypA activated ERK1/2 and p38 MAPK signaling pathways and increased the secretion of 2 key cytokines IL‐5 and IL‐17 in Panc‐1 cells.CONCLUSIONSThe expression of CypA and CD147 was significantly increased in both pancreatic cancer cell lines and tissues. Exogenous CypA promotes pancreatic cancer cell growth, which may be mediated through the interaction with CD147 and the activation of ERK1/2 and p38 MAPKs. Cancer 2006. © 2006 American Cancer Society.

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“…CD147 expression is elevated on several human tumors and has been correlated with the malignancy in some cancers such as primary breast cancer and ovarian cancer, etc. (7)(8)(9)(10)(11)(12). Despite the close correlation between CD147 expression and malignancy of some tumors, it is not clear whether CD147 has a functional role in tumor genesis and hepatocellular carcinoma (HCC) progression.…”

Section: Introductionmentioning

confidence: 99%

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

Xu¹,

Xu²,

Zhang³

et al. 2007

Molecular Cancer Research

143

134

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CD147 molecule is reported to be correlated with the malignancy of some cancers; however, it remains unclear whether it is involved in the progression of hepatocellular carcinoma (HCC). Here, we investigated the function of HAb18G/CD147, a member of CD147 family, and its antibodies, HAb18 and LICARTIN, in HCC invasion and metastasis. We observed that HAb18G/CD147 gene silence in HCC cells significantly decreased the secretion of matrix metalloproteinase (MMP) and the invasive potential of HCC cells (P < 0.001). MMP silence in HCC cells also significantly suppressed the invasion of the cells when cocultured with fibroblasts; however, its inhibitory effect was significantly weaker than that of both HAb18G/CD147 silence in HCC cells and that of MMP silence in fibroblasts (P < 0.001). Blocking the HAb18G/CD147 molecule on HCC cells with HAb18 monoclonal antibody resulted in a similar suppressive effect on MMP secretion and cell invasion, but with no significant effects on the cell growth. 131 I-labeled HAb18 F(ab ¶) 2 (LICARTIN), however, significantly inhibited the in vitro growth of HCC cells (P < 0.001). In an orthotopic model of HCC in nude mice, HAb18 and LICARTIN treatment effectively reduced the tumor growth and metastasis as well as the expression of three major factors in the HCC microenviroment (MMPs, vascular endothelial growth factor, and fibroblast surface protein) in the paracancer tissues. Overall, these results suggest that HAb18G/CD147 plays an important role in HCC invasion and metastasis mainly via modulating fibroblasts, as well as HCC cells themselves to disrupt the HCC microenviroment. LICARTIN can be used as a drug targeting to HAb18G/ CD147 in antimetastasis and recurrence therapy of HCC.

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Expression of emmprin (CD147), a cell surface inducer of matrix metalloproteinases, in normal human brain and gliomas

Cited by 136 publications

References 38 publications

High incidence of EMMPRIN expression in human tumors

High incidence of EMMPRIN expression in human tumors

Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

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