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

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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
Volume57
Issue number12
Publication statusPublished - Jun 15 1997

    Fingerprint

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.