The lutheran/basal cell adhesion molecule promotes tumor cell migration by modulating integrin-mediated cell attachment to laminin-511 protein

J Biol Chem. 2013 Oct 25;288(43):30990-1001. doi: 10.1074/jbc.M113.486456. Epub 2013 Sep 13.

Abstract

Cell-matrix interactions are critical for tumor cell migration. Lutheran (Lu), also known as basal cell adhesion molecule (B-CAM), competes with integrins for binding to laminin α5, a subunit of LM-511, a major component of basement membranes. Here we show that the preferential binding of Lu/B-CAM to laminin α5 promotes tumor cell migration. The attachment of Lu/B-CAM transfectants to LM-511 was slightly weaker than that of control cells, and this was because Lu/B-CAM disturbed integrin binding to laminin α5. Lu/B-CAM induced a spindle cell shape with pseudopods and promoted cell migration on LM-511. In addition, blocking with an anti-Lu/B-CAM antibody led to a flat cell shape and inhibited migration on LM-511, similar to the effects of an activating integrin β1 antibody. We conclude that tumor cell migration on LM-511 requires that Lu/B-CAM competitively modulates cell attachment through integrins. We suggest that this competitive interaction is involved in a balance between static and migratory cell behaviors.

Keywords: Cell Adhesion; Cell Migration; Extracellular Matrix; Integrin; Invasion; Laminin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane / metabolism
  • Basement Membrane / pathology
  • Cell Adhesion / genetics
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Shape
  • HEK293 Cells
  • Humans
  • Integrins / genetics
  • Integrins / metabolism*
  • Laminin / genetics
  • Laminin / metabolism*
  • Lutheran Blood-Group System / genetics
  • Lutheran Blood-Group System / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Knockout
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology

Substances

  • BCAM protein, human
  • Bcam protein, mouse
  • Cell Adhesion Molecules
  • Integrins
  • Laminin
  • Lutheran Blood-Group System
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • laminin alpha5