Aberrant ADAM10 expression correlates with osteosarcoma progression

European Journal of Medical Research

Aimin Wang¹  Bing Ni²  Yi Tian²  Dongjing Ni²  Ren Zhao¹ 

[1] Department of Orthopedics, Daping Hospital, Third Military Medical University, No. 10 Changjiang Road, Daping, Yuzhong District, Chongqing 400042, China;Institute of Immunology of PLA, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China

关键词: Tumor progression;    Osteosarcoma;    Osteoclast;    Notch1;    Multinucleated giant cell;    CD31;    ADAM10;   

Others  :  817606
DOI  :  10.1186/2047-783X-19-9

 received in 2013-09-09, accepted in 2014-02-07,  发布年份 2014

【 摘 要 】

Background

Osteosarcoma is the most common type of bone cancer and is notorious for its rapid progression. The Notch signaling pathway has recently been shown to be involved in osteosarcoma. As a major sheddase of Notch receptors, ADAM10 has been implicated in many types of cancers, but its role in osteosarcoma has not been investigated. Previous studies have shown that the expression of CD31 was significantly elevated in metastatic osteosarcoma; however, its expression in nonmetastatic groups is not known. In addition, the mysterious multinucleated giant cell in giant cell-rich osteosarcoma was previously regarded as an osteoclast-like cell, but its exact identity is unclear.

Method

Tissue chip samples from 40 cases of nonmetastatic osteosarcoma were stained for cytoplasmic ADAM10, activated Notch1 and CD31. Osteoclasts in tumor sections were also stained for tartrate-resistant acid phosphatase (TRAP).

Results

Immunofluorescence staining revealed that ADAM10 expression significantly increased with the progression of osteosarcoma as well as in osteoblastic osteosarcoma, whereas the expression of the Notch intracellular domain (NICD) and CD31 was not significantly altered between different pathological stages. In addition, multinucleated giant cells in giant cell-rich osteosarcoma were also found to coexpress CD31, ADAM10 and NICD, but were negative for TRAP staining.

Conclusions

Our results highlight the importance of ADAM10 in the progression of osteosarcoma and suggest that the protein might be a potential therapeutic target in osteosarcoma treatment. This study also demonstrates that the multinucleated giant cell is an angiogenic tumor cell, rather than an osteoclast, and involves ADAM10/Notch1 signaling activation.

【 授权许可】

   
2014 Zhao et al.; licensee BioMed Central Ltd.

【 图 表 】

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