Pro-adhesive and chemotactic activities of thrombospondin-1 for breast carcinoma cells are mediated by alpha3beta1 integrin and regulated by insulin-like growth factor-1 and CD98

J Biol Chem. 1999 Apr 16;274(16):11408-16. doi: 10.1074/jbc.274.16.11408.


Thrombospondin-1 (TSP1) is a matricellular protein that displays both pro- and anti-adhesive activities. Binding to sulfated glycoconjugates mediates most high affinity binding of soluble TSP1 to MDA-MB-435 cells, but attachment and spreading of these cells on immobilized TSP1 is primarily beta1 integrin-dependent. The integrin alpha3beta1 is the major mediator of breast carcinoma cell adhesion and chemotaxis to TSP1. This integrin is partially active in MDA-MB-435 cells but is mostly inactive in MDA-MB-231 and MCF-7 cells, which require beta1 integrin activation to induce spreading on TSP1. Integrin-mediated cell spreading on TSP1 is accompanied by extension of filopodia containing beta1 integrins. TSP1 binding activity of the alpha3beta1 integrin is not stimulated by CD47-binding peptides from TSP1 or by protein kinase C activation, which activate alphavbeta3 integrin function in the same cells. In MDA-MB-231 but not MDA-MB-435 cells, this integrin is activated by pertussis toxin, whereas serum, insulin, insulin-like growth factor-1, and ligation of CD98 increase activity of this integrin in both cell lines. Serum stimulation is accompanied by increased surface expression of CD98, whereas insulin-like growth factor-1 does not increase CD98 expression. Thus, the pro-adhesive activity of TSP1 for breast carcinoma cells is controlled by several signals that regulate activity of the alpha3beta1 integrin.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antigens, CD / physiology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carrier Proteins / physiology*
  • Cell Adhesion / physiology
  • Chemotaxis / physiology
  • Fusion Regulatory Protein-1
  • GTP-Binding Proteins / metabolism
  • Humans
  • Insulin-Like Growth Factor I / physiology*
  • Integrin alpha3beta1
  • Integrins / physiology*
  • Protein Binding
  • Protein Conformation
  • Signal Transduction
  • Thrombospondin 1 / chemistry
  • Thrombospondin 1 / metabolism
  • Thrombospondin 1 / physiology*
  • Tumor Cells, Cultured


  • Antigens, CD
  • Carrier Proteins
  • Fusion Regulatory Protein-1
  • Integrin alpha3beta1
  • Integrins
  • Thrombospondin 1
  • Insulin-Like Growth Factor I
  • GTP-Binding Proteins