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

• Published in: Pathology, research and practice research and practice, 2023-05, Vol.245, p.154443-154443, Article 154443
• Main Authors: Mori, Natsumi, Esaki, Nobutoshi, Shimoyama, Yoshie, Shiraki, Yukihiro, Asai, Naoya, Sakai, Tomohisa, Nishida, Yoshihiro, Takahashi, Masahide, Enomoto, Atsushi, Mii, Shinji
• Format: Article
• Language: English
• Subjects: Antigens, CD - metabolism; BMP; Bone Neoplasms; CD109; GPI-Linked Proteins - metabolism; Humans; Neoplasm Proteins - metabolism; Neoplastic Processes; Osteosarcoma; Prognostic marker; SMAD; Transforming Growth Factor beta - metabolism
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2023.154443

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. •CD109 is highly expressed in osteosarcoma cells and tissue.•CD109 is a statistically significant poor prognostic factor in human osteosarcoma.•CD109 negatively regulates BMP signaling in osteosarcoma cells.•CD109 suppresses BMP-2-mediated cell migration in osteosarcoma.