Extracellular matrix metalloproteinase inducer (EMMPRIN) expression correlates positively with active angiogenesis and negatively with basic fibroblast growth factor expression in epithelial ovarian cancer

Abstract

PurposeThe primary aim of this paper was to evaluate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its relationship with proangiogenic factors and microvessel density (MVD) in ovarian cancer.MethodsThe study group included 58 epithelial ovarian cancers (EOCs), 35 benign ovarian tumors, and 21 normal ovaries. The expression of EMMPRIN, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) was assessed by ELISA of tissue homogenates. Antibodies against CD105, CD31, and CD34 were used to immunohistochemically assess MVD.ResultsWe have found significantly higher EMMPRIN expression in EOC than in benign ovarian tumors and normal ovaries. Similarly, the VEGF expression was higher in EOC than in benign ovarian tumors and normal ovaries. By contrast, bFGF expression was lower in EOC than in benign ovarian tumors and ovary samples. EMMPRIN expression in EOC was directly correlated with VEGF expression and CD105-MVD, but inversely correlated with bFGF expression. Grade 2/3 ovarian cancers had increased expression of EMMPRIN and VEGF, increased CD105-MVD, and lowered expression of bFGF compared to grade 1 ovarian cancers. Moreover, EMMPRIN expression was higher in advanced (FIGO III and IV) ovarian cancer.ConclusionsThe upregulation of EMMPRIN and VEGF expression is correlated with increased CD105-MVD and silenced bFGF, which suggests early and/or reactivated angiogenesis in ovarian cancer. Aggressive EOC is characterized by the following: high expression of EMMPRIN and VEGF, high CD105-MVD, and low expression of bFGF.

Selective Inhibition of the Lactate Transporter MCT4 Reduces Growth of Invasive Bladder Cancer

“…Currently, there are 14 different members of the MCT protein family (6). MCT1 and MCT4 as well as their chaperone CD147 have been shown to be overexpressed in a variety of cancer types (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Moreover, an association of these proteins with outcome has been identified in several tumors (9,(18)(19)(20)(21).…”

CD147 modulates androgen receptor activity through the Akt/Gsk-3β/β-catenin/AR pathway in prostate cancer cells

“…C D147, a lso k now n a s ext r a c el lu la r mat r i x metalloproteinase inducer (EMMPRIN), is highly expressed on the surface of the majority of cancer cells (11). During tumorigenesis, CD147 contributes to metastasis, drug resistance and angiogenesis (12)(13)(14) invasion, metastasis and autophagy (12,15). In addition, CD147 regulates the canonical Wnt/β-catenin signaling pathway to accelerate lung tumorigenesis (16).…”

The associations between serum VEGF, bFGF and endoglin levels with microvessel density and expression of proangiogenic factors in malignant and benign ovarian tumors

“…We have also presented previously higher CD105-MVD in malignant than in benign ovarian tumors (Szubert et al, 2014). Lowered bFGF expression in malignant when compared to benign ovarian tumors we have demonstrated and discussed earlier (Szubert et al, 2014).…”

“…Increased tumor expression of several proangiogenic factors, like vascular-endothelial growth factor (VEGF) suggests shortened survival in ovarian cancer (Han et al, 2010;Yu et al, 2013;Smerdel et al, 2009). On the other hand, lowered bFGF expression may indicate high grade epithelial ovarian cancers (Szubert et al, 2014).…”