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

• Published in: International journal of oncology Vol. 52; no. 4; pp. 1255 - 1266
• Main Authors: Iwasawa, Taiji, Zhang, Pu, Ohkawa, Yuki, Momota, Hiroyuki, Wakabayashi, Toshihiko, Ohmi, Yuhsuke, Bhuiyan, Robiul H, Furukawa, Keiko, Furukawa, Koichi
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01-04-2018; Spandidos Publications UK Ltd
• Subjects: Brain cancer; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Care and treatment; Cell Line, Tumor; Cell Movement - physiology; Cell Proliferation - physiology; Chemotherapy; Development and progression; Gangliosides - metabolism; Gene expression; Genetic aspects; Glioma; Glioma - metabolism; Glioma - pathology; Gliomas; Growth factors; Health aspects; Humans; Immunoglobulins; Kinases; Ligands; Medical prognosis; Melanoma; Neoplasm Invasiveness - pathology; Neuroblastoma; Oncogenes; Radiation therapy; Studies; Transcription factors; Tumor Cells, Cultured; United States > US; Japan
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2018.4266

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.