Contact guidance of Walker carcinosarcoma cells by the underlying normal fibroblasts is inhibited by RGD-containing synthetic peptides.
The metastatic spread of malignant neoplasms is associated with active migration of cancer cells. The migration of neoplastic cells during the metastatic process may be affected by various extracellular factors, including chemoattractants, haptotactic signals, electric fields, substrate anisotropy, and cell-to-cell contacts. We examined the effect of homotypic collisions and heterotypic interactions with normal human skin fibroblasts on the motile activity of Walker carcinosarcoma cells. It was found that Walker carcinosarcoma cells moving in a dense population neither show contact inhibition of movement when colliding with one another nor increase their motile activity as a result of contact stimulation of motility. On the other hand, when plated onto the surface of aligned fibroblasts, Walker carcinosarcoma cells migrated mainly along the long axes of underlying fibroblasts as a result of contact guidance. The directional character of movement (but not the speed of migration) of Walker carcinosarcoma cells on the surface of aligned fibroblasts was completely effaced by RGD-containing synthetic peptide at a concentration of 1 mg/ml but not by 5 microM verapamil (selective voltage-gated calcium channel inhibitor) or 10 microM gadolinium chloride (non-specific blocker of mechanosensitive ion channels). The suppression of directional character of migration of tumour cells by RGD-containing peptide was associated with the decrease in the amount of fibronectin macromolecules attached to fibroblasts. This suggests that alignment and anisotropic distribution of fibronectin macromolecules may be responsible for contact guidance of tumour cells moving on the surface of fibroblasts.
Madeja
Zbigniew
Z
Department of Cell Biology, The Jan Zurzycki Institute of Molecular Biology and Biotechnology, Jagiellonian University, Cracow, Poland. Zibi@mol.uj.edu.pl
Sroka
Jolanta
J
D000595:Amino Acid Sequence; D000818:Animals; D002279:Carcinoma 256, Walker / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology*; D011137:Polystyrenes; D051381:Rats; D014407:Tumor Cells, Cultured
D009842:Oligopeptides; D011137:Polystyrenes; C047981:arginyl-glycyl-aspartic acid