Oligosaccharide modification by swainsonine treatment inhibits pulmonary colonization by B16-F10 murine melanoma cells.
Oligosaccharide moieties of cell-surface glycoconjugates are thought to be involved in recognition events associated with tumor metastasis and invasion. Using swainsonine (SW), an inhibitor of Golgi alpha-mannosidase II that results in the formation of hybrid-type oligosaccharides on N-linked glycoproteins, we have tested the hypothesis that specific glycan structures are required for pulmonary colonization by tumor cells. B16-F10 murine melanoma cells were treated with SW in growth medium and then injected intravenously into syngeneic C57BL/6 mice. This treatment resulted in dramatic inhibition of colonization, but it had no effect on B16-F10 viability or on cellular tumorigenicity after subcutaneous implantation. SW-treated radiolabeled B16-F10 cells were cleared from the lungs at a greater rate than control cells, suggesting that one effect of treatment is to alter tumor cell retention in the target organ. Our results implicate specific glycan structures in pulmonary colonization and offer a potential approach for identification of specific macromolecules involved in tumor cell-organ recognition during metastasis.
Humphries
M J
MJ
Matsumoto
K
K
White
S L
SL
Olden
K
K
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D006023:Glycoproteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D008361:Mannosidases / Q000037:antagonists & inhibitors; D008545:Melanoma / Q000517:prevention & control / Q000556:secondary*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009844:Oligosaccharides / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017026:Swainsonine
D000470:Alkaloids; D006023:Glycoproteins; D008565:Membrane Proteins; D009844:Oligosaccharides; D008361:Mannosidases; C038829:mannosyl-oligosaccharide 1,3 - 1,6-alpha-mannosidase; D017026:Swainsonine