Endosialin/CD248 may be a potential therapeutic target to prevent the invasion and metastasis in osteosarcoma

内皮唾液酸蛋白/CD248可能是阻止骨肉瘤侵袭和转移的潜在治疗靶点

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作者:Yumiko Kondo, Kanya Honoki, Shingo Kishi, Shiori Mori, Rina Fujiwara-Tani, Shinji Tsukamoto, Hiromasa Fujii, Hiroki Kuniyasu, Yasuhito Tanaka

Abstract

Endosialin/CD248/tumor endothelial marker 1 is classified as a C-type lectin-like transmembrane receptor, found on the plasma membrane of activated mesenchymal cells, which binds to fibronectin. Although endosialin is expressed at high levels in stem-like cells of sarcomas, its role has not been fully uncovered. The present study aimed to determine whether endosialin expression is associated with tumor progression and metastasis, and whether endosialin has the potential to act as a novel therapeutic target in osteosarcoma (OS) using MORAb-004/ontuxizumab, a humanized monoclonal antibody, which targets the type C lectin domain of endosialin. The results demonstrated that endosialin was highly expressed in OSs with metastatic disease. Furthermore, MORAb-004 had no cytostatic effect on OS cells in vitro and did not change the expression of stem cells and differentiation markers; however, it inhibited migration of OS cells. Taken together, these results suggest that endosialin may play a role in migration, and may be involved in the metastatic process of OSs. Furthermore, MORAb-004 reduces the motility of OS cells, and suppresses invasion and the development of metastatic lesions.

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