The function and distinctive regulation of the integrin VLA-3 in cell adhesion, spreading, and homotypic cell aggregation

Jonathan B. Weitzman, Renata Pasqualini, Yoshikazu Takada, Martin E. Hemler

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137 Citations (Scopus)

Abstract

To assess directly the functional role of the integrin VLA-3 (α3β1), we transfected human α3 cDNA into erythroleukemia (K562) cells and rhabdomyosarcoma (RD) cells. The resulting transfectants (KA3 and RA3) expressed α3β1 on the cell surface as confirmed using a panel of nine anti-α3 monoclonal antibodies. Neither of the transfected cells exhibited increased adhesion to the extracellular matrix proteins fibronectin, laminin, and collagen. However, the KA3 transfectants did bind strongly to the extracellular matrix deposited by epidermal and carcinoma cell lines, allowing the cells to attach and spread. Binding to this cell-deposited ligand, probably containing epiligrin/kalinin, was specific to VLA-3 and could be inhibited by anti-α3 antibodies and by EDTA, but not by RGD peptides. In marked contrast to other integrins (VLA-2 and VLA-4), VLA-3 showed high constitutive activity in K562 cells, but was minimally active in RD cells. Also con trasting with other β1 integrins, VLA-3 was minimally stimulated by the anti-β1 monoclonal antibody TS/216 under normal conditions. VLA-3-mediated adhesive function was well supported by either Mg2+ or Mn2+, but was almost completely abolished by the presence of 1 mM Ca2+. Surprisingly, this negative Ca2+ effect was completely overcome by the addition of the stimulatory anti-β1 monoclonal antibody TS2/16. Together, these results point to markedly distinct regulation for VLA-3 function compared to other β1 integrins. Also, all anti-VLA-3 antibodies were able to induce temperature-dependent homotypic cell aggregation of KA3 cells, but not K562 cells. However, this aggregation did not appear to be directly mediated by VLA-3 since it was not inhibited by EDTA. In addition, no enhancement of heterotypic cell-cell adhesion was observed in α3-transfected cells.

Original languageEnglish
Pages (from-to)8651-8657
Number of pages7
JournalJournal of Biological Chemistry
Volume268
Issue number12
Publication statusPublished - Apr 25 1993
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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