Modulation of haptotactic migration of metastatic melanoma cells by the interaction between heparin and heparin-binding domain of fibronectin.
We utilized recombinant fibronectin polypeptides with cell-binding domain and heparin-binding domains (referred to as C-274 and H-271, respectively) and their fusion polypeptide (CH-271) to examine the role of sulfated polysaccharide heparin and/or the functional domains of fibronectin in modulating tumor cell behavior. Both C-274 and CH-271 polypeptides with cell-binding domains promoted the adhesion and migration of B16-BL6 melanoma cells, whereas H-271 did not. Heparin bound to the immobilized polypeptides with heparin-binding domain (H-271, CH-271, and a mixture of C-274 and H-271 or fibronectin) but did not affect the tumor cell adhesion to the substrates. At the same time, heparin or two monoclonal antibodies against the heparin-binding domain were able to inhibit the haptotactic migration to CH-271 or fibronectin, though not to C-274 or a mixture of C-274 and H-271. This suggests that although heparin did not affect tumor cell adhesion to the cell-binding domain near the heparin-binding domain in CH-271 or fibronectin, it did lead to a modulation of cell motility. It seems likely that the regulatory mechanism may depend on interaction between heparin-like molecules on the cell surface and the heparin-binding domain in fibronectin, rather than on simple steric hindrance or on the masking of the cell-binding domain caused by the binding of heparin to heparin-binding domain.
Makabe
T
T
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Saiki
I
I
Murata
J
J
Ohdate
Y
Y
Kawase
Y
Y
Taguchi
Y
Y
Shimojo
T
T
Kimizuka
F
F
Kato
I
I
Azuma
I
I
D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology*; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D010446:Peptide Fragments / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology*
D005353:Fibronectins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006493:Heparin