Open AccessEnhancement of malignant properties of human osteosarcoma cells with disialyl gangliosides GD 2/ GD 3
Author(s) -
Shibuya Hidenobu,
Hamamura Kazunori,
Hotta Hiroshi,
Matsumoto Yasuyuki,
Nishida Yoshihiro,
Hattori Hisashi,
Furukawa Keiko,
Ueda Minoru,
Furukawa Koichi
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02344.x
Subject(s) - paxillin , lyn , phosphorylation , tyrosine phosphorylation , transfection , motility , cancer research , tyrosine kinase , focal adhesion , cell culture , ganglioside , osteosarcoma , chemistry , kinase , microbiology and biotechnology , proto oncogene tyrosine protein kinase src , biology , signal transduction , biochemistry , genetics
The expression and implications of gangliosides in human osteosarcomas have not been systematically analyzed. In this study, we showed that gangliosides GD 3 and GD 2 are highly expressed in the majority of human osteosarcoma cell lines derived from oral cavity regions. Introduction of GD 3 synthase cDNA into a GD 3/ GD 2‐negative ( GD 3/ GD 2−) human osteosarcoma subline resulted in the establishment of GD 3/ GD 2+ transfectant cells. They showed increased cell migration and invasion activities in wound healing and B oyden chamber invasion assays, respectively, compared to the control cells. When treated with serum, GD 3/ GD 2+ cells showed stronger tyrosine phosphorylation of p130 C as, focal adhesion kinase, and paxillin than GD 3/ GD 2− cells. In particular, paxillin underwent much stronger phosphorylation, suggesting its role in cell motility. Furthermore, we tried to dissect the roles of GD 3 and GD 2 in the malignant properties of the transfectant cells by establishing single ganglioside‐expressing cells, that is, either GD 3 or GD 2. Although GD 3/ GD 2+ cells showed the most malignant properties, GD 2+ cells showed almost equivalent levels to GD 3/ GD 2+ cells in invasion and migration activities, and in the intensities of tyrosine phosphorylation of paxillin. Among S rc family kinases, L yn was expressed predominantly, and was involved in the invasion and motility of GD 3‐ and/or GD 2‐expressing transfectants. Furthermore, it was elucidated by gene silencing that L yn was located in a different pathway from that of FAK to eventually lead paxillin activation. These results suggested that GD 2/ GD 3 are responsible for the enhancement of the malignant features of osteosarcomas, and might be candidate targets in molecular‐targeted therapy.