Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin.

Published

Journal Article

The development of pulmonary metastasis is the major cause of death in osteosarcoma, and its molecular basis is poorly understood. In this study, we show that beta4 integrin is highly expressed in human osteosarcoma cell lines and tumor samples. Furthermore, highly metastatic MNNG-HOS cells have increased levels of beta4 integrin. Suppression of beta4 integrin expression by shRNA and disruption of beta4 integrin function by transfection of dominant-negative beta4 integrin was sufficient to revert this highly metastatic phenotype in the MNNG-HOS model without significantly affecting primary tumor growth. These findings suggest a role for beta4 integrin expression in the metastatic phenotype in human osteosarcoma cells. In addition, we identified a previously uncharacterized interaction between beta4 integrin and ezrin, a membrane-cytoskeletal linker protein that is implicated in the metastatic behavior of osteosarcoma. The beta4 integrin-ezrin interaction appears to be critical for maintenance of beta4 integrin expression. These data begin to integrate ezrin and beta4 integrin expression into a model of action for the mechanism of osteosarcoma metastases.

Full Text

Duke Authors

Cited Authors

  • Wan, X; Kim, SY; Guenther, LM; Mendoza, A; Briggs, J; Yeung, C; Currier, D; Zhang, H; Mackall, C; Li, W-J; Tuan, RS; Deyrup, AT; Khanna, C; Helman, L

Published Date

  • September 2009

Published In

Volume / Issue

  • 28 / 38

Start / End Page

  • 3401 - 3411

PubMed ID

  • 19597468

Pubmed Central ID

  • 19597468

Electronic International Standard Serial Number (EISSN)

  • 1476-5594

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/onc.2009.206

Language

  • eng