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The high affinity alphaIIb beta3 integrin is involved in invasion of human melanoma cells.

Abstract
Integrins play an important role in mediating tumor cell-extracellular matrix (ECM) and tumor cell-endothelial cell interactions. The integrin alphaIIb beta3 (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 alphaIIb beta3 integrin. Reverse transcription-PCR/Southern blotting, Northern blotting, and dot blotting demonstrated the presence of the platelet-type alphaIIb beta3 integrin in human melanoma WM 983B, WM 983A, and WM 35 cells. AP-2, a monoclonal antibody (mAb) to alphaIIb beta3, 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 alphaIIb beta3. PAC-1 specifically recognizes the conformationally active form of platelet alphaIIb beta3. 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 alphaIIb beta3 integrin but not the Fc receptor. Confocal immunofluorescent studies demonstrated that fibronectin-adherent melanoma cells possess an intracellularly localized pool of high-affinity alphaIIb beta3. 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 alphaIIb beta3 integrin, which is involved in tumor invasion.
AuthorsM Trikha, J Timar, S K Lundy, K Szekeres, Y Cai, A T Porter, K V Honn
JournalCancer research (Cancer Res) Vol. 57 Issue 12 Pg. 2522-8 (Jun 15 1997) ISSN: 0008-5472 [Print] United States
PMID9192835 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antibodies, Monoclonal
  • Epitopes
  • Fibronectins
  • Oligopeptides
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • RNA, Messenger
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • arginyl-glycyl-aspartic acid
  • Tetradecanoylphorbol Acetate
Topics
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid (pharmacology)
  • Adult
  • Antibodies, Monoclonal (pharmacology)
  • Blotting, Northern
  • Blotting, Southern
  • Cell Adhesion (drug effects)
  • Epitopes (metabolism)
  • Female
  • Fibronectins (metabolism)
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Immunohistochemistry
  • Melanoma (metabolism, pathology)
  • Microscopy, Confocal
  • Neoplasm Invasiveness
  • Oligopeptides (pharmacology)
  • Platelet Glycoprotein GPIIb-IIIa Complex (metabolism)
  • RNA, Messenger (metabolism)
  • Tetradecanoylphorbol Acetate (pharmacology)
  • Tumor Cells, Cultured (drug effects)

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