RRC ID |
74991
|
Author |
Mori N, Esaki N, Shimoyama Y, Shiraki Y, Asai N, Sakai T, Nishida Y, Takahashi M, Enomoto A, Mii S.
|
Title |
Significance of expression of CD109 in osteosarcoma and its involvement in tumor progression via BMP signaling.
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Journal |
Pathol Res Pract
|
Abstract |
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.
|
Volume |
245
|
Pages |
154443
|
Published |
2023-5-1
|
DOI |
10.1016/j.prp.2023.154443
|
PII |
S0344-0338(23)00143-7
|
PMID |
37030166
|
MeSH |
Antigens, CD* / metabolism
Bone Neoplasms*
GPI-Linked Proteins / metabolism
Humans
Neoplasm Proteins* / metabolism
Neoplastic Processes
Osteosarcoma*
Transforming Growth Factor beta / metabolism
|
IF |
2.05
|
Resource |
Human and Animal Cells |
MG-63(RCB1890)
Saos-2(RCB0428) |