Significance of expression of CD109 in osteosarcoma and its involvement in tumor progression via BMP signaling

Natsumi Mori, Nobutoshi Esaki, Yoshie Shimoyama, Yukihiro Shiraki, Naoya Asai, Tomohisa Sakai, Yoshihiro Nishida, Masahide Takahashi, Atsushi Enomoto, Shinji Mii

研究成果: ジャーナルへの寄稿学術論文査読

抄録

Osteosarcoma, the most common primary malignant bone tumor, is defined by the formation of neoplastic osteoid and/or bone. This sarcoma is a highly heterogeneous disease with a wide range of patient outcomes. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed in various types of malignant tumors. We previously reported that CD109 is expressed in osteoblasts and osteoclasts in normal human tissues and plays a role in bone metabolism in vivo. While CD109 has been shown to promote various carcinomas through the downregulation of TGF-β signaling, the role and mechanism of CD109 in sarcomas remain largely unknown. In this study, we investigated the molecular function of CD109 in sarcomas using osteosarcoma cell lines and tissue. Semi-quantitative immunohistochemical analysis using human osteosarcoma tissue revealed a significantly worse prognosis in the CD109-high group compared with the CD109-low group. We found no association between CD109 expression and TGF-β signaling in osteosarcoma cells. However, enhancement of SMAD1/5/9 phosphorylation was observed in CD109 knockdown cells under bone morphogenetic protein-2 (BMP-2) stimulation. We also performed immunohistochemical analysis for phospho-SMAD1/5/9 using human osteosarcoma tissue and found a negative correlation between CD109 expression and SMAD1/5/9 phosphorylation. In vitro wound healing assay showed that osteosarcoma cell migration was significantly attenuated in CD109-knockdown cells compared with control cells in the presence of BMP. These results suggest that CD109 is a poor prognostic factor in osteosarcoma and affects tumor cell migration via BMP signaling.

本文言語英語
論文番号154443
ジャーナルPathology Research and Practice
245
DOI
出版ステータス出版済み - 05-2023

All Science Journal Classification (ASJC) codes

  • 病理学および法医学
  • 細胞生物学

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