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Disialyl gangliosides enhance tumor phenotypes with differential modalities

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Abstract

Sialic acid-containing glycosphingolipids, gangliosides are highly expressed in human cancer cells and regulate cell signals transduced via membrane microdomains. Generally, disialyl gangliosides enhance tumor phenotypes, while monosialyl gangliosides suppress them. In particular, gangliosides GD3 and GD2 are highly expressed in melanomas and small cell lung cancer cells, and their expression cause increased cell growth and invasion. In osteosarcomas, expression of GD3 and GD2 also enhanced cell invasion and motility, and caused increased phosphorylation of focal adhesion kinase and paxillin. In addition to focal adhesion kinase, Lyn kinase was also activated by GD3/GD2 expression, leading to the phosphorylation of paxillin. In contrast with melanoma cells, osteosarcomas showed reduced cell adhesion with increased phosphorylation of paxillin. Thus, increased expression of GD3/GD2 caused enhanced activation of signaling molecules, leading to distinct phenotypes between melanomas and osteosarcomas, i.e. increased and decreased adhesion activity. Thus, whole features of glycolipid-enriched microdomain/rafts formed in the individual cancer types seem to determine the main signaling pathway and biological outcome.

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Acknowledgments

We thank H. Shibuya and H. Hotta for valuable discussion, and T. Mizuno and Y. Nakayasu for technical assistance. This study was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports and Technology in Japan (MEXT).

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There is no conflict of interest.

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Authors and Affiliations

  1. Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-0065, Japan

    Koichi Furukawa, Kazunori Hamamura, Yuki Ohkawa, Yuhsuke Ohmi & Keiko Furukawa

  2. Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto-cho, Kasugai, 487-8501, Japan

    Keiko Furukawa

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  1. Koichi Furukawa
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  2. Kazunori Hamamura
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Correspondence to Koichi Furukawa.

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Furukawa, K., Hamamura, K., Ohkawa, Y. et al. Disialyl gangliosides enhance tumor phenotypes with differential modalities. Glycoconj J 29, 579–584 (2012). https://doi.org/10.1007/s10719-012-9423-0

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  • DOI: https://doi.org/10.1007/s10719-012-9423-0

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