Enhancement of malignant properties of human glioma cells by ganglioside GD3/GD2

Iwasawa,Taiji; Zhang,Pu; Ohkawa,Yuki; Momota,Hiroyuki; Wakabayashi,Toshihiko; Ohmi,Yuhsuke; Bhuiyan,Robiul  H.; Furukawa,Keiko; Furukawa,Koichi

doi:10.3892/ijo.2018.4266

Enhancement of malignant properties of human glioma cells by ganglioside GD3/GD2

Authors:
- Taiji Iwasawa
- Pu Zhang
- Yuki Ohkawa
- Hiroyuki Momota
- Toshihiko Wakabayashi
- Yuhsuke Ohmi
- Robiul H. Bhuiyan
- Keiko Furukawa
- Koichi Furukawa
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Affiliations: Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan, Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai, Aichi 487-8501, Japan, Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Published online on: February 7, 2018 https://doi.org/10.3892/ijo.2018.4266
Pages: 1255-1266

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Abstract

Sialic acid-containing glycosphingolipids, gangliosides, are considered as cancer associated antigens in neuro-ectoderm-derived tumors such as melanomas and neuroblastomas. In particular, gangliosides GD3 and GD2 are expressed in human gliomas. It has been reported that their expression levels increase along with increased malignant properties. However, the implication of GD3/GD2 in human glioma cells has never been clarified, at least to the best of our knowledge. In this study, we introduced the cDNA of GD3 synthase (GD3S)(ST8SIA1) into a glioma cell line, U-251MG, that expresses neither GD3 nor GD2, thereby establishing transfectant cells U-251MG-GD3S(+) expressing high levels of GD3 and GD2 on the cell surface. In these U-251MG‑GD3S(+) cell lines, signaling molecules such as Erk1/2, Akt, p130Cas, paxillin and focal adhesion kinase were activated, leading to the enhancement of invasion activity and motility. It was then demonstrated that the U-251MG-GD3S(+) cells could proliferate under culture conditions with low or no serum concentrations without undergoing cell cycle arrest by escaping the accumulation of p16 and p21. All these results suggested that GD3 and GD2 highly expressed in gliomas confer increased invasion and mobility, cell growth abilities under low serum conditions, and increased ratios of the S-G2/M phase in the cell cycle.

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