EMMPRIN expression is associated with metastatic progression in osteosarcoma

Abstract

Background Extracellular matrix metalloproteinase inducer (EMMPRIN), a cell-surface glycoprotein, is overexpressed in several cancer types. EMMPRIN induces a metastatic phenotype by triggering the production of matrix metalloproteinase proteins (MMPs) such as MMP1 and MMP2, and vascular endothelial growth factor (VEGF) in cancer cells and the surrounding stromal cells. The purpose of this study was to investigate the expression and role of EMMPRIN in osteosarcoma. Methods The level of EMMPRIN expression was evaluated using reverse transcriptase polymerase chain reaction (RT-PCR) in 6 tumor-derived osteosarcoma cell lines and compared with that in normal osteoblasts. To study the prognostic significance of EMMPRIN expression, immunohistochemistry was carried out in prechemotherapy biopsies of 54 patients. siRNA knockdown of EMMPRIN in SaOS-2 cells was conducted to explore the role of EMMPRIN. To study the role of EMMPRIN in tumor-stromal interaction in MMP production and invasion, co-culture of SaOS-2 cells with osteoblasts and fibroblasts was performed. Osteosarcoma 143B cells were injected into the tail vein of BALB/c mice and lung metastasis was analyzed. Results EMMRIN mRNA expression was significantly higher in 5 of 6 (83%) tumor-derived cells than in MG63 cells. 90% of specimens (50/54) stained positive for EMMPRIN by immunohistochemistry, and higher expression of EMMPRIN was associated with shorter metastasis-free survival (p = 0.023). Co-culture of SaOS-2 with osteoblasts resulted in increased production of pro-MMP2 and VEGF expression, which was inhibited by EMMPRIN-targeting siRNA. siRNA knockdown of EMMPRIN resulted in decreased invasion. EMMPRIN shRNA-transfected 143B cells showed decreased lung metastasis in vivo. Conclusions Our data suggest that EMMPRIN acts as a mediator of osteosarcoma metastasis by regulating MMP and VEGF production in cancer cells as well as stromal cells. EMMPRIN could serve as a therapeutic target in osteosarcoma.

Pan-Cancer Analysis, Reveals COVID-19-Related BSG as a Novel Marker for Treatment and Identification of Multiple Human Cancers

“…Our study revealed differences in the BSG expression levels in various human organs and cancer cells. In terms of tissues, previous reports have identified differently expressed BSG in a few cancers, such as melanoma (Kim et al, 2021;Lu et al, 2021) and LIHC (Wang SJ et al, 2020). In our study, compared with normal tissues, BSG mRNA was highly expressed in cancers containing BLCA, BRCA, CHOL, ESCA, HNSCC, KICH, KIRP, LIHC, LUAD, and LUSC, PRAD, STAD, THCA, and UCEC, while it was lowly expressed in COAD and READ.…”

“…In addition to COVID-19, BSG is also reported to be involved in the tumorigenesis of multiple tumors, such as melanoma (Kim et al, 2021;Lu et al, 2021), liver hepatocellular carcinoma (LIHC) (Wang SJ et al, 2020), and hypopharyngeal squamous cell carcinoma (Suzuki et al, 2021). BSG has been found to induce the degradation of the extracellular matrix through the matrix metalloproteinase proteins and stimulates the vascular endothelial growth factor, thus participating in the invasion and metastasis of tumors (Weidle et al, 2010;Kim et al, 2021). It is also reported that T cells and NK cells carrying a chimeric antigen receptor that recognizes BSG is detrimental to the tumor cell lines in vitro (Tseng et al, 2020).…”

The updated role of exosomal proteins in the diagnosis, prognosis, and treatment of cancer

“…The ability of tissue-derived exosomes to carry tumor promoters and initiate ECM remodeling in the TME is critical for the survival of tumor cells. Exosomal proteins (e.g., extracellular matrix metalloproteinase inducer) have been found to induce ECM remodeling by activating the generation of MMPs in fibroblasts 66 . MMPs can remodel the ECM by disassembling it and releasing the embedded growth factors, thereby facilitating tumor growth and metastasis.…”

Matrix Metalloproteinases and Their Inhibitors in Pulmonary Fibrosis: EMMPRIN/CD147 Comes into Play

“…In addition, expression has been found in various malignancies such as laryngeal carcinomas [280], breast carcinomas [281], lymphoma [282], hepatoma [283], and malignant pigment cell lesions [284]. Recent studies associate CD147 expression with metastatic progression in osteosarcoma [285] and describe CD147 as a promising marker for the detection of circulating tumor cells in Small Cell Lung Cancer [286]. Furthermore, the discovery of CD147 in non-tumoral tissues suggests that it may have a role in other physiological and pathological circumstances producing increased MMP expression.…”