Identification of a tumor cell receptor for VGVAPG, an elastin-derived chemotactic peptide.
Extracellular matrix proteins and their proteolytic products have been shown to modulate cell motility. We have found that certain tumor cells display a chemotactic response to degradation products of the matrix protein elastin, and to an elastin-derived peptide, VGVAPG. The hexapeptide VGVAPG is a particularly potent chemotaxin for lung-colonizing Lewis lung carcinoma cells (line M27), with 5 nM VGVAPG eliciting maximal chemotactic response when assayed in 48-microwell chemotaxis chambers. Binding of the elastin-derived peptide to M27 cells was studied using a tyrosinated analog (Y-VGVAPG) to allow iodination. Scatchard analysis of [125I]Y-VGVAPG binding to viable M27 tumor cells at both 37 and 4 degrees C indicates the presence of a single class of high affinity binding sites. The dissociation constant obtained from these studies (2.7 X 10(-9) M) is equivalent to the concentration of VGVAPG required for chemotactic activity. The receptor molecule was identified as an Mr 59,000 species by covalent cross-linking of the radiolabeled ligand to the M27 tumor cell surface and subsequent analysis of the cross-linked material by electrophoresis and size-exclusion high performance liquid chromatography. These results suggest that M27 tumor cell chemotaxis to VGVAPG is initiated by high affinity binding of the peptide to a distinct cell surface receptor.
Blood
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CH
Department of Cellular Physiology, Children's Hospital, Boston, MA 02115.
Sasse
J
J
Brodt
P
P
Zetter
B R
BR
D000818:Animals; D002630:Chemotactic Factors / Q000378:metabolism*; D003432:Cross-Linking Reagents; D004549:Elastin / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002630:Chemotactic Factors; D003432:Cross-Linking Reagents; D009363:Neoplasm Proteins; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D004549:Elastin; C042635:valyl-glycyl-valyl-alanyl-prolyl-glycine