alexa GM3 ganglioside inhibits CD9-facilitated haptotactic cell motility: coexpression of GM3 and CD9 is essential in the downregulation of tumor cell motility and malignancy.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Glycomics & Lipidomics

Author(s): Ono M, Handa K, Sonnino S, Withers DA, Nagai H,

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Abstract A cooperative inhibitory effect of GM3, together with CD9, on haptotactic cell motility was demonstrated by a few lines of study as described below. (i) Haptotactic motility of colorectal carcinoma cell lines SW480, SW620, and HRT18, which express CD9 at a high level, is inhibited by exogenous GM3, but not by GM1. (ii) Motility of gastric cancer cell line MKN74, which expresses CD9 at a low level, was not affected by exogenous GM3. Its motility became susceptible to and inhibited by exogenous GM3, but not GM1, when the CD9 level of MKN74 cells was converted to a high level by transfection with CD9 cDNA. Findings i and ii suggest that haptotactic tumor cell motility is cooperatively inhibited by coexpression of CD9 and GM3. (iii) This possibility was further demonstrated using cell line ldlD 14, and its derivative expressing CD9 through transfection of its gene (termed ldlD/CD9). Both of these cell lines are defective in UDP-Gal 4-epimerase and cannot synthesize GM3 unless cultured in the presence of galactose (Gal(+)), whereas GM3 synthesis does not occur when cells are cultured in the absence of Gal (Gal(-)). Haptotactic motility of parental ldlD cells is low, and shows no difference in the presence and absence of Gal. In contrast, the motility of ldlD/CD9 cells is very high in Gal(-) whereby endogenous GM3 synthesis does not occur, and is very reduced in Gal(+) whereby endogenous GM3 synthesis occurs. (iv) Photoactivatable (3)H-labeled GM3 added to HRT18 cells, followed by UV irradiation, causes cross-linking of GM3 to CD9, as evidenced by (3)H labeling of CD9, which is immunoprecipitated with anti-CD9 antibody. These findings suggest that CD9 is a target molecule interacting with GM3, and that CD9 and GM3 cooperatively downregulate tumor cell motility.
This article was published in Biochemistry and referenced in Journal of Glycomics & Lipidomics

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