The high affinity αIIbβ3 integrin is involved in invasion of human melanoma cells

Mohit Trikha, Jozsef Timar, Steven K. Lundy, Karoly Szekeres, Yinlong Cai, Arthur T. Porter, Kenneth V. Honn

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Integrins play an important role in mediating tumor cell-extracellular matrix (ECM) and tumor cell-endothelial cell interactions. The integrin αIIβ3 (GPIIb-IIIa) is expressed on the surface of platelets in an inactive state and requires a conformational change to recognize extracellular matrix proteins such as fibrinogen, fibronectin, vitronectin, and others. In this study, we questioned whether human melanoma cells express the αIIbβ3 integrin. Reverse transcription-PCR/Southern blotting, Northern blotting, and dot blotting demonstrated the presence of the platelet-type αIIbβ3 integrin in human melanoma WM 983B, WM 983A, and WM 35 cells. AP-2, a monoclonal antibody (mAb) to αIIbβ3, positively stained two human melanoma specimens, indicating expression of this integrin in vivo. Phorbol 12-myristate 13- acetate and 12(S)-hydroxyeicosatetraenoic acid, two activators of protein kinase C, stimulated adhesion of melanoma cells to immobilized fibronectin and PAC-1, a mAb to αIIbβ3. PAC-1 specifically recognizes the conformationally active form of platelet αIIbβ3. Phorbol 12-myristate 13- acetate-stimulated adhesion of WM 983B cells to PAC-1 was completely blocked by an RGD peptide, thus providing evidence that tumor cell adhesion to PAC-1 is mediated via the αIIbβ3 integrin but not the Fe receptor. Confocal immunofluorescent studies demonstrated that fibronectin-adherent melanoma cells possess an intracellularly localized pool of high-affinity αIIbβ3. Invasion of WM 983B cells through fibronectin was stimulated by 12(S)- hydroxyeicosatetraenoic acid, and this stimulated invasion was blocked by the mAb PAC-1. The data suggest that melanoma cells express the high-affinity αIIbβ3 integrin, which is involved in tumor invasion.

Original languageEnglish
Pages (from-to)2522-2528
Number of pages7
JournalCancer Research
Issue number12
Publication statusPublished - Jun 15 1997


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Trikha, M., Timar, J., Lundy, S. K., Szekeres, K., Cai, Y., Porter, A. T., & Honn, K. V. (1997). The high affinity αIIbβ3 integrin is involved in invasion of human melanoma cells. Cancer Research, 57(12), 2522-2528.