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Expression and function of the high affinity αIibβ3 integrin in murine melanoma cells

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Abstract

In resting platelets integrin αIibβ3 is constitutively expressed in an inactive state and it does not recognize soluble proteins. Platelet activation results in a conformational change of the low-affinity αIibβ3 to a high-affinity state which then recognizes plasma fibrinogen. The ectopic expression of αIibβ3 integrin in rodent and human cells derived from solid tumors is well documented, although little is known about its affinity state in these tumor cells. In this study we analysed expression and function of high-affinity αIibβ3 in murine metastatic melanoma B16a cells by using a mAb that specifically recognizes high-affinity αIibβ3 (PAC-1). These tumor cells while in suspension bound PAC-1 and fibrinogen. Immunofluorescent studies of B16a cells indicated that high-affinity αIibβ3 is associated with the Golgi complex and the cell surface. Stimulation of B16a cells with a PKC-activator, 12(S)-HETE, induced translocation of the high-affinity integrin from an intracellular pool to the plasma membrane, which resulted in increased tumor cell adhesion to fibronectin. In addition to participating in 12(S)-HETE-stimulated adhesion of B16a cells, the high-affinity aIIbb3 inte-grin is also involved in tumor cell invasion through a reconstituted basement membrane. In conclusion, results from this study suggest that in non-megakaryocytic lineage B16a cells αIibβ3 is constitutively expressed in a high-affinity state, and that this conformation participates in tumor cell adhesion and invasion. © Rapid Science Ltd.

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Authors and Affiliations

  1. First Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, Hungary

    Jozsef Timar

  2. Department of Radiation Oncology, Wayne State University, Detroit, MI, USA

    Mohit Trikha, Karoly Szekeres & Rajesh Bazaz

  3. Department of Pathology, Wayne State University, Detroit, MI, USA

    Kenneth Honn

Authors
  1. Jozsef Timar
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  2. Mohit Trikha
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  3. Karoly Szekeres
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  4. Rajesh Bazaz
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  5. Kenneth Honn
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Timar, J., Trikha, M., Szekeres, K. et al. Expression and function of the high affinity αIibβ3 integrin in murine melanoma cells. Clin Exp Metastasis 16, 437–445 (1998). https://doi.org/10.1023/A:1006533508560

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  • DOI: https://doi.org/10.1023/A:1006533508560

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