B7-H3 is overexpressed in patients suffering osteosarcoma and associated with tumor aggressiveness and metastasis

PLoS One. 2013 Aug 5;8(8):e70689. doi: 10.1371/journal.pone.0070689. Print 2013.

Abstract

B7-H3 is a member of the B7-family of co-stimulatory molecules, which has been shown to be broadly expressed in various tumor tissues, and which plays an important role in adaptive immune responses. The role of B7-H3 in osteosarcoma, however, remains unknown. In this study we used immunohistochemistry to analyze B7-H3 expression in 61 primary osteosarcoma tissues with case-matched adjacent normal tissues, and 37 osteochondroma and 20 bone fibrous dysplasia tissues. B7-H3 expression was expressed in 91.8% (56/61) of the osteosarcoma lesions, and the intensity of B7-H3 expression in osteosarcoma was significantly increased compared with adjacent normal tissues, osteochondroma and bone fibrous dysplasia tissues (p<0.001). Patients with high tumor B7-H3 levels had a significantly shorter survival time and recurrence time than patients with low tumor B7-H3 levels (p<0.001). Moreover, tumor B7-H3 expression inversely correlated with the number of tumor-infiltrating CD8(+) T cells (p<0.05). In vitro, increasing expression of B7-H3 promotes osteosarcoma cell invasion, at least in part by upregulating matrix metalloproteinase-2 (MMP-2). In conclusion, our study provides the first evidence of B7-H3 expression in osteosarcoma cells as a potential mechanism controlling tumor immunity and invasive malignancy, and which is correlated with patients' survival and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7 Antigens / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Bone Neoplasms / immunology
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferon-gamma / metabolism
  • Kaplan-Meier Estimate
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Neoplasm Recurrence, Local / metabolism*
  • Osteosarcoma / immunology
  • Osteosarcoma / metabolism*
  • Osteosarcoma / mortality
  • Osteosarcoma / secondary
  • Young Adult

Substances

  • B7 Antigens
  • Biomarkers, Tumor
  • CD276 protein, human
  • Interferon-gamma
  • MMP2 protein, human
  • Matrix Metalloproteinase 2

Grant support

This work was financially supported by Grants from Medical Research Project of Hebei Provincial Health Department (20110481). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.