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  P3.01 - Poster Session 3 - Cancer Biology (ID 147)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

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    P3.01-019 - Analysis of Integrins in Malignant Mesothelioma (MM). (ID 1147)

    09:30 - 09:30  |  Author(s): N.C. Cheng
    • Abstract

    Background
    Malignant mesothelioma (MM), strongly associated with exposure to asbestos, is a growing worldwide problem (1). This aggressive tumour is largely resistant to oncological treatments and new approaches to therapy are urgently needed. Integrins are a class of adhesion molecules composed of an α and a β chain. Combinations of 18 α and 8 β subunits form the 24 members of the integrin family. The αv subunit can dimerize with β1, β3, β5, β6 and β8. Aberrant expression of αv integrins was reported in MM, and the integrins αv β3 and αv β5 have been implicated in tumour progression and metastasis. We have investigated the expression and function of αv integrins in MM cell lines and the effect of gene knockdown on cell invasion.

    Methods
    Expression of the integrin (ITG) genes was analysed by qPCR in 7 MM cell lines. Expression of the heterodimers was determined by Western blot, immunofluorescence and immunocytometry (monoclonal antibodies kindly provided by Simon Goodman, 2). In addition, we knocked down the genes potentially involved in tumour progression (ITGB3 and ITGB5) and analysed the in vitro 2D and 3D invasiveness with an agarose spot invasion assay (3) and MM spheroids.

    Results
    All 7 MM cell lines showed high ITGB1 expression, moderate ITGB5 expression, and a general low ITGB6 and ITGB8 expression. ITGB3 was expressed in one cell line, which accordingly had high αv β3 expression. ITGB3 knockdown of this cell line resulted in suppression of invasion both in 2D and 3D cultures.

    Conclusion
    We have found evidence that integrin αv β3 may play a role in MM invasion. Presently, we are testing cilengitide, a peptide antagonist of integrin αv, in MM cell lines. References: 1. Delgermaa F, Takahashi K, Park EK, Le GV, Hara T, Sorahan T. Global mesothelioma deaths reported to the World Health Organization between 1994 and 2008. Bull World Health Organ. 2011, 89:716-724. 2. Goodman SL, Grote HJ, Wilm C. Matched rabbit monoclonal antibodies against αv-series integrins reveal a novel αvβ3-LIBS epitope, and permit routine staining of archival paraffin samples of human tumors. Biol Open. 2012, 1:329-340. 3. Wiggins H and Rappoport J. An agarose spot assay for chemotactic invasion. Biotechniques. 2010, 48:121-124.