title: Inhibition of b16 melanoma metastasis by administration of g(m3)- or gg3- liposomes - blocking adhesion of melanoma-cells to endothelial-cells (antiadhesion therapy) via inhibition of g(m3)-gg3cer or g(m3)-laccer interaction.
abstract: Tumor cell (TC) metastasis is initiated by selective adhesion of TCs to target structures such as basement membrane and endotheliaI cells (ECs), followed by transvascular migration of TCs. Variants of murine B16 melanoma having different metastatic potentials (in the order BL6 greater than or equal to F10>F1>WA4) have been characterized by the same decreasing order of cell surface G(M3) expression level, relative adhesiveness to nonactivated ECs, and relative degree of G(M3)-dependent adhesion to Gg3Cer- or LacCer-coated plates. Degree of integrin-dependent cell adhesion and adhesion to IL-1-activated ECs was similar for BL6, F10, and F1. These results suggest that metastatic potential of these B16 variants is closely dependent on relative adhesion to nonactivated ECs, which is based on G(M3)-Gg3Cer or G(M3)-LacCer interaction. This possibility has been supported by further studies showing that blocking of G(M3)-dependent melanoma adhesion by mu M-order concentrations of G(M3) or Gg3Cer in liposomes, or by sialidase treatment of melanoma cells, strongly inhibited BL6 metastasis to lung. Paragloboside or sialylparagloboside did not affect G(M3)-dependent BL6 cell adhesion and did not inhibit metastasis. Spontaneous metastasis from subcutaneously-grown tumors was significantly reduced if G(M3)- or Gg3Cer-liposomes were intravenously injected during tumor growth. Thus, blocking of TC adhesion to nonactivated ECs based on carbohydrate-carbohydrate interaction may provide effective anti-adhesion therapy against tumor progression, in analogy to the antimetastatic effect produced by blocking of integrin-dependent cell adhesion.
authors.affiliation: BIOMEMBRANE INST,SEATTLE,WA 98119. UNIV WASHINGTON,DEPT PATHOBIOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MICROBIOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT CHEM,SEATTLE,WA 98195.
authors.forename: E
authors.initials: E
authors.lastname: Otsuji
authors.forename: Y
authors.initials: Y
authors.lastname: Park
authors.forename: K
authors.initials: K
authors.lastname: Tashiro
authors.forename: N
authors.initials: N
authors.lastname: Kojima
authors.forename: T
authors.initials: T
authors.lastname: Toyokuni
authors.forename: S
authors.initials: S
authors.lastname: Hakomori