Kondo Yumiko, Honoki Kanya, Kishi Shingo, Mori Shiori, Fujiwara-Tani Rina, Tsukamoto Shinji, Fujii Hiromasa, Kuniyasu Hiroki, Tanaka Yasuhito
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara 634-8521, Japan.
Department of Orthopedic Oncology and Reconstructive Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan.
Oncol Lett. 2022 Feb;23(2):42. doi: 10.3892/ol.2021.13160. Epub 2021 Dec 6.
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 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.
内涎蛋白/CD248/肿瘤内皮标志物1被归类为一种C型凝集素样跨膜受体,存在于活化间充质细胞的质膜上,可与纤连蛋白结合。尽管内涎蛋白在肉瘤的干细胞样细胞中高表达,但其作用尚未完全阐明。本研究旨在确定内涎蛋白的表达是否与肿瘤进展和转移相关,以及使用靶向内涎蛋白C型凝集素结构域的人源化单克隆抗体MORAb-004/ontuxizumab,内涎蛋白是否有潜力作为骨肉瘤(OS)的新型治疗靶点。结果表明,内涎蛋白在伴有转移的骨肉瘤中高表达。此外,MORAb-004对骨肉瘤细胞没有细胞抑制作用,也未改变干细胞和分化标志物的表达;然而,它抑制了骨肉瘤细胞的迁移。综上所述,这些结果表明内涎蛋白可能在迁移中起作用,并且可能参与骨肉瘤的转移过程。此外,MORAb-004降低了骨肉瘤细胞的运动性,并抑制转移灶的侵袭和发展。