title: Aberrant ADAM10 expression correlates with osteosarcoma progression.
abstract: 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.
  
  
  METHODS
  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.
authors.forename: Ren
authors.initials: R
authors.lastname: Zhao
authors.forename: Dongjing
authors.initials: D
authors.lastname: Ni
authors.forename: Yi
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Orthopedics, Daping Hospital, Third Military Medical University, No, 10 Changjiang Road, Daping, Yuzhong District, Chongqing 400042, China. nibingxi@yahoo.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Ni
authors.forename: Aimin
authors.initials: A
authors.lastname: Wang
mesh_terms: D051722:ADAM Proteins / Q000032:analysis / Q000096:biosynthesis*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005455:Fluorescent Antibody Technique; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human