CMG2 Expression Is an Independent Prognostic Factor for Soft Tissue Sarcoma Patients

Abstract

The capillary morphogenesis gene 2 (CMG2), also known as the anthrax toxin receptor 2 (ANTXR2), is a transmembrane protein putatively involved in extracellular matrix (ECM) adhesion and tissue remodeling. CMG2 promotes endothelial cell proliferation and exhibits angiogenic properties. Its downregulation is associated with a worsened survival of breast carcinoma patients. Aim of this study was to analyze the CMG2 mRNA and protein expression in soft tissue sarcoma and their association with patient outcome. CMG2 mRNA was measured in 121 tumor samples of soft tissue sarcoma patients using quantitative real-time PCR. CMG2 protein was evaluated in 52 tumor samples by ELISA. CMG2 mRNA was significantly correlated with the corresponding CMG2 protein expression (rs = 0.31; p = 0.027). CMG2 mRNA expression was associated with the mRNA expressions of several ECM and tissue remodeling enzymes, among them CD26 and components of the uPA system. Low CMG2 mRNA expression was correlated with a worsened patients’ disease-specific survival in Kaplan-Meier analyses (mean patient survival was 25 vs. 96 months; p = 0.013), especially in high-stage tumors. A decreased CMG2 expression is a negative prognostic factor for soft tissue sarcoma patients. CMG2 may be an interesting candidate gene for the further exploration of soft tissue sarcoma genesis and progression.

Knockdown of Kif20a inhibits growth of tumors in soft tissue sarcoma in vitro and in vivo

“…The capillary morphogenesis gene 2 (CMG2) has been demonstrated to promote endothelial cell proliferation and exhibits angiogenic properties. In STSs, low CMG2 expression was correlated with a worsened prognosis 18 . In this study, we found that high Kif20 a expression predicted poor prognosis, which is a new finding.…”

Current understanding of Bacillus anthracis toxin molecules organization and approaches for blocking their cytotoxic action

“…TEM8 еще называют рецептором сибирской язвы 1 (Anthrax Toxin Receptor -ATR1), CMG2 -рецептором сибирской язвы 2 (ATR2). Основные функции белков ТЕМ8 и CMG2 заключаются в том, что они являются молекулами клеточной адгезии и вовлечены в ангиогенез [4,16]. Экспрессия CMG2 наблюдается в большинстве человеческих тканей, а ТЕМ8 экспрессируется главным образом на опухолевых эндотелиальных и раковых клетках [16,22].…”

“…Основные функции белков ТЕМ8 и CMG2 заключаются в том, что они являются молекулами клеточной адгезии и вовлечены в ангиогенез [4,16]. Экспрессия CMG2 наблюдается в большинстве человеческих тканей, а ТЕМ8 экспрессируется главным образом на опухолевых эндотелиальных и раковых клетках [16,22]. CMG2, ТЕМ8 и β1интегрин относятся к трансмембранным белкам типа 1, имеющим высококонсервативный внеклеточный домен фактора фон Виллебранда типа А, который связывается непосредственно с ПА.…”

B. anthracis protective antigen: a molecular imaging agent targeting squamous cell carcinoma

“…CMG2 has been suggested to be an oncogene of glioma, increasing in expression with clinical grade (28). Conversely, CMG2 is inversely correlated to progression and survival in breast cancer (29) and soft tissue sarcoma (30). The function of CMG2 in tumour development appears to be more complex than TEM8, the decreased expression observed in breast cancer may be a factor in its invasiveness and metastatic potential while overexpression in glioma may promote angiogenesis.…”

“…PA mediates the binding and translocation of anthrax toxins into cells (103) through highly specific interactions with two conserved anthrax toxin receptors (61,104). These receptors have been identified to be selectively overexpressed on a variety of tumour tissues (28,30,39), thus are potential biomarkers of cancer. PA has the potential to be developed as a tumour targeting agent for diagnostic or therapeutic purposes, and has been previously demonstrated to target toxins to tumours in preclinical models (72,73).…”