Association of extracellular matrix metalloproteinase inducer in endometrial carcinoma with patient outcomes and clinicopathogenesis using monoclonal antibody 12C3

Yamada, Kyosuke; Urashima, Mitsuyoshi; Ishibashi, Yoshio; Shirai, Misako; Nikaido, Takashi; Takahashi, Hiroyuki; Okamoto, Aikou; Saito, Misato; Yasuda, Makoto; Ohkawa, Kiyoshi; Tanaka, Tadao

doi:10.3892/or.17.4.731

Cited by 16 publications

(18 citation statements)

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“…Accordingly, emmprin expression has been found to be associated with known risk factors for breast cancer and with a poor prognosis of breast cancer patients [19]. In endometrial cancer, Ueda et al reported that high levels of emmprin expression had a significant association with recurrence [33]. However, the correlation between emmprin expression and survival has not been studied in endometrial cancer.…”

Section: Discussionmentioning

confidence: 99%

Role of emmprin in endometrial cancer

et al. 2012

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BackgroundExtracellular 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.MethodsEmmprin 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.ResultsThe 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.ConclusionsThe 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.

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Section: Discussionmentioning

confidence: 99%

Role of emmprin in endometrial cancer

et al. 2012

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“…Esophageal squamous cell carcinomas (ESCC) (stage 3 and 4) and endometrial (97.3% incidence) carcinoma show significant upregulation of tissue expression of CD147, while CD147 is not expressed in the respective normal tissues [130,131]. CD147 holds promise as a reliable biomarker in cancer progression, showing a significant expression increase in carcinomas compared with sarcomas and normal epithelial tissues, as well as positively correlating with tumor recurrence and progression and negatively correlating to survival in breast cancer patients in a retrospective study [132].…”

Section: Cd147 and Cancermentioning

confidence: 99%

Tumor Metabolism of Lactate: The Influence and Therapeutic Potential for MCT and CD147 Regulation

2009

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Tumor metabolism consists of complex interactions between oxygenation states, metabolites, ions, the vascular network and signaling cascades. Accumulation of lactate within tumors has been correlated with poor clinical outcomes. While its production has negative implications, potentially contributing to tumor progression, the implications of the ability of tumors to utilize lactate can offer new therapeutic targets for the future. Monocarboxylate transporters (MCTs) of the SLC16A gene family influence substrate availability, the metabolic path of lactate and pH balance within the tumor. CD147, a chaperone to some MCT subtypes, contributes to tumor progression and metastasis. The implications and consequences of lactate utilization by tumors are currently unknown; therefore future research is needed on the intricacies of tumor metabolism. The possibility of metabolic modification of the tumor microenvironment via regulation or manipulation of MCT1 and CD147 may prove to be promising avenues of therapeutic options. KeywordsCancer; CD147; lactate; MCT1; MCT1 inhibitors; MCT4; tumor metabolism Much of the past research on lactate in cancer has focused on its production. Under the influence of hypoxia, glucose is catabolized to lactate via glycolysis to yield ATP; mitochondria cannot produce ATP in oxidative phosphorylation without oxygen to aid in electron transport. This type of production is termed the 'Pasteur effect.' Cancer cells can also produce lactate under aerobic conditions. The switch from a 'normal' metabolic profile, consisting of glycolysis followed by oxidative phosphorylation, to cytosolic glycolysis in the presence of adequate oxygen, is termed the 'Warburg effect.' The discovery of aerobic glycolysis resulting in increased lactate production within tumors in the 1920-1930s by Otto Warburg led to a reevaluation of the potential role and significance of lactate in cancer studies [1][2][3][4]. Since the pioneering work of Warburg, production and accumulation of lactate has been documented to have clinical significance in a number of different cancer types. In the 1970s, lactate metabolism in malignant metastatic carcinomas and colorectal cancers was beginning to be explored with blood samples from patients that were injected or infused with radio-labeled glucose and pyruvate [5,6]. These studies indicated that lactate levels in plasma and venous †Author NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript blood were elevated in patients with metastatic cancer [6]. Nuclear magnetic resonance (NMR) studies following the fate of 13 C-labeled lactate are still used today.In the 1980s, quantitative bioluminescence imaging was used to assess metabolites such as lactate and glucose from flash-frozen biopsies to study ischemia in brain tissue [7,8]. This technique was later applied to assess these same metabolites in cancer [9][10][11]. More recent studies investigating lactate accumulation in human tumors have found that cervical tumors, head and neck cancers and rectal adenoc...

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“…EMMPRIN, also called CD147 or basigin, is a cellular adhesion molecule involved in cell-cell and cell-ECM interactions (8–10). EMMPRIN is highly expressed on the surface of various malignant tumor cells compared with their normal counterparts (16,17) and is involved in tumor invasion and metastasis (14,18). Our previous study found that overexpression of EMMPRIN was a prognostic factor for patients with SACC and was positively associated with the perineural and perivascular invasion of SACC (11).…”

Section: Discussionmentioning

confidence: 99%

EMMPRIN contributes to the in vitro invasion of human salivary adenoid cystic carcinoma cells

Yang

Zhang²,

Ma³

et al. 2011

Oncology Reports

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Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that is involved in tumor invasion by stimulating matrix metalloproteinase (MMP) expression. Our previous immunohistochemical study found that the expression of EMMPRIN in salivary adenoid cystic carcinoma (SACC) was positively correlated with tumor perineural and perivascular invasion. The present study was designed to further investigate the role of EMMPRIN in the invasion of SACC. Western blot results showed that EMMPRIN was upregulated in the highly metastatic SACC cell line SACC-LM, compared to SACC-83, a SACC cell line with low metastatic ability. Blocking of EMMPRIN by its antibody significantly decreased the adhesion, secretion of MMP-2 and MMP-9, and invasion activity of SACC-LM cells in vitro (P<0.01). Co-cultures of SACC-LM cells with fibroblasts significantly produced elevated levels of MMP-2 and MMP-9, and promoted the in vitro invasion activity of SACC-LM cells, compared with cultures of SACC-LM cells alone (P<0.01). These results indicate that EMMPRIN may play an important role in the invasion of SACC by stimulating the expression of MMP-2 and MMP-9 in tumor and stromal cells.

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Association of extracellular matrix metalloproteinase inducer in endometrial carcinoma with patient outcomes and clinicopathogenesis using monoclonal antibody 12C3

Cited by 16 publications

References 15 publications

Role of emmprin in endometrial cancer

Role of emmprin in endometrial cancer

Tumor Metabolism of Lactate: The Influence and Therapeutic Potential for MCT and CD147 Regulation

EMMPRIN contributes to the in vitro invasion of human salivary adenoid cystic carcinoma cells

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