Identification of a Tumor Cell Receptor for VGVAPG, an Elastin-Derived Chemotactic Peptide

• Published in: The Journal of cell biology 1988-11, Vol.107 (5), p.1987-1993
• Main Authors: Blood, Christine H., Sasse, Joachim, Brodt, Pnina, Zetter, Bruce R.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell adhesion; Cell receptors; Cell structures and functions; Cell surface receptors; Cells; chemotactic factors; Chemotactic Factors - metabolism; Cross-Linking Reagents; elastin; Elastin - metabolism; Endothelial cells; Fibroblasts; Fundamental and applied biological sciences. Psychology; Ligands; Lung Neoplasms - metabolism; Molecular and cellular biology; Molecular Weight; Neoplasm Proteins - metabolism; Oligopeptides - metabolism; Radioactive decay; Receptors; Receptors, Cell Surface - metabolism; Tumor cell line; Tumor Cells, Cultured; Tumors
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.107.5.1987

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°C indicates the presence of a single class of high affinity binding sites. The dissociation constant obtained from these studies (2.7× 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.