Correlation of inhibition of adhesion of large cell lymphoma and hepatic sinusoidal endothelial cells by RGD-containing peptide polymers with metastatic potential: role of integrin-dependent and -independent adhesion mechanisms.
Murine RAW117 large-cell lymphoma cells that show organ preferences of metastatic colonization were selected. We examined the role of adhesive systems in determining the organ preference of metastasis using cell lines of low (RAW117-P) and high (RAW117-H10) liver-metastatic potential. Highly metastatic H10 cells adhered at higher rates than low metastatic P cells to target organ microvessel endothelial cells, and these interactions were partially inhibited by RGD-containing polymers but not by small peptides such as GRGDS or GRGES. The most effective polymers, such as (GRGDS)4 and GRGDS(GRGES)2GRGDS, significantly inhibited H10 cell adhesion but had less effect on P cell adhesion to target liver sinusoidal endothelial cell monolayers or on P cell or H10 cell adhesion to bovine aortic endothelial cell monolayers. The (GRGDS)4 polymer reduced the rate of H10 liver sinusoidal endothelial cell adhesion to that of P cells in the absence of inhibitors, suggesting that the quantitative difference in adhesion of H10 cells versus P cells to liver sinusoidal endothelial cells may have been due to integrin-like molecules. Other RGD-containing polymers, such as (GRGES)2(GRGDS)2, GRGES(GRGDS)2GRGES, or (GRGES)4, were less effective, suggesting that the secondary structure of the polymers may be an important consideration. A peptide from the B1 chain of laminin (YIGSR) or its homopolymer, (YIGSR)4, had no effect on endothelial cell adhesion, consistent with the lack of differential laminin adhesion seen with various RAW117 cell lines. The results suggest that integrin-related molecules may play a role in the organ specificity of endothelial cell adhesion seen with RAW117 tumor cells.
Tressler
R J
RJ
Department of Tumor Biology, University of Texas MD Anderson Cancer Center, Houston 77030.
Belloni
P N
PN
Nicolson
G L
GL
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D016023:Integrins / Q000502:physiology*; D007700:Kinetics; D008102:Liver Circulation; D008113:Liver Neoplasms / Q000556:secondary; D008223:Lymphoma; D051379:Mice; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D010455:Peptides / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D016023:Integrins; D010455:Peptides