Chemotaxis of the M27 variant of
Lewis lung carcinoma to
VGVAPG, an
elastin-derived
chemoattractant, is restricted by the basement membrane
glycoprotein laminin.
Laminin does not inhibit random migration of M27
tumor cells, nor does it inhibit M27 cell chemotaxis to a second chemotactic
peptide, fMLF. The
laminin sensitivity of
VGVAPG chemotaxis appears to be independent of adhesion to
laminin, and it is not due to competitive inhibition of
VGVAPG receptor binding. Preincubation of M27 cells with
laminin reduces the affinity of
VGVAPG-specific binding without altering the number of available
VGVAPG receptors. Reduced
VGVAPG receptor affinity was previously observed: (a) a nonresponsive
Lewis lung carcinoma variant, H59, expresses low-affinity
VGVAPG binding and (b) maintenance of high-affinity
VGVAPG receptors on M27
tumor cells is correlated with elevated
protein kinase C activity in the particulate cell fraction (C. H. Blood and B. R. Zetter, J. Biol. Chem., 264: 10614-10620, 1989). The negative regulation of
VGVAPG chemotaxis by
laminin is consistent with these observations:
laminin coordinately inhibits
VGVAPG chemotaxis, reduces
VGVAPG receptor affinity, and decreases
protein kinase C activity in the particulate fraction of M27 cells. These parameters are not affected by a second
glycoprotein,
fibronectin. Anti-alpha 6
antibodies neutralize the
laminin inhibition of both
VGVAPG chemotaxis and
protein kinase C activity. The results demonstrate that
laminin can modulate cell behavior by regulating
cell surface receptors for biologically active
ligands.