Expression patterns of emmprin and monocarboxylate transporter-1 in ovarian epithelial tumors

Abstract

Emmprin is a transmembrane glycoprotein known as a matrix metalloproteinase inducer and is highly up-regulated in malignant cancer cells. The monocarboxylate transporters (MCTs) are responsible for H(+)-linked transport of monocarboxylates across the cell membrane. It was recently demonstrated that proper plasma membrane localization and activity of MCTs require the presence of emmprin as a chaperone and that MCT-1 also acts as chaperone for emmprin. The objectives of this study were to clarify emmprin and MCT-1 expression patterns in ovarian epithelial tumors and to elucidate the clinicopathological significance of co-localization of the two molecules. Immunohistochemical analysis of 205 epithelial tumors indicated that emmprin is always localized in cell membranes but its distribution differs according to tumor type: in lateral membranes in 89 % of adenomas, in lateral and basal membranes in 76 % of borderline tumors, and in membranes surrounding the entire cell in 98 % of carcinomas. Most carcinomas in situ also showed a lateral and basal expression pattern. In only 21 % of the carcinomas, the cells expressing membranous MCT-1 showed co-localized emmprin expression. Poor co-localization of the two molecules was more frequently found in serous carcinomas. However, the overall survival was not significantly different for the good and poor co-localization carcinoma groups. These findings indicate that the emmprin expression pattern might discriminate between invasive carcinomas and borderline tumors including carcinoma in situ. Moreover, there may be an as yet unidentified regulatory mechanism(s), for localization of MCT-1 and emmprin in cell membranes in vivo.

Basigin-2 is the predominant basigin isoform that promotes tumor cell migration and invasion and correlates with poor prognosis in epithelial ovarian cancer

“…Importantly, its expression is often correlated with tumor metastasis and poor prognosis [10-18]. There are already papers showing that basigin is associated with the survival and progression of ovarian cancer, and is considered as a biomarker of poor outcome [39-41]. However, some results show that basigin is a significant indicator of a favorable prognosis of ovarian cancer [42,43].…”

The Biological Function and Clinical Utilization of CD147 in Human Diseases: A Review of the Current Scientific Literature

“…Interestingly, CD147 expression is often concurrent with other factors involved in the pathological process, such as MCTs. Good colocalization of CD147 and MCT1 has been found in 23 carcinomas by identical immunostaining scores [9]. Furthermore, an immunohistochemical examination of the plasma membranes of MLS-175 soft tissue sarcoma cells revealed that 40% of samples were positive for CD147 and 60% were positive for MCTs (MCT1 and MCT4) [55].…”

“…Many different human cancers over-express CD147 on tumor cell surfaces, including several common cancers (Table 1) and giant cell tumors [49], synoviocytes [50], cancer stem cells (CSCs) [51], and human multiple myeloma cell lines (HMCLs) [52]. Other investigators have found that CD147 is expressed in the membranous and/or cytoplasmic compartments of ovarian carcinoma [9,53]. Moreover, the CD147 expression level is not related to the age of the cancer patient, tumor type or gross morphology but is related to tumor histopathologic type and clinical stage of disease [52,54].…”

“…Under hypoxic conditions, CD147 promotes tumor growth, inhibits tumor cell apoptosis and enhances the invasion ability of malignant tumors, thus, CD147 may contribute to the Warburg effect. Under a hypoxic microenvironment, malignant tumor cells rapidly reproduce, using glycolysis for energy, and excessive lactate must be transported by MCTs for tumor cell survival [9], while the lactic acid production is harmful to most normal host cells [10,11]. …”

EMMPRIN Promotes Angiogenesis, Proliferation, Invasion and Resistance to Sunitinib in Renal Cell Carcinoma, and Its Level Predicts Patient Outcome

“…MCTs are responsible for H + -linked transport of monocarboxylates across the cell membrane. It was recently demonstrated that proper plasma membrane localization and activity of MCTs require the presence of EMMPRIN as a chaperone and that MCT-1 acts as chaperone for EMMPRIN [45]. Indeed, this study showed that silencing of EMMPRIN decreased MCT1 expression and abolished the co-localization of EMMPRIN and MCT1.…”