RRC ID 58663
Author Sasaki N, Hirabayashi K, Michishita M, Takahashi K, Hasegawa F, Gomi F, Itakura Y, Nakamura N, Toyoda M, Ishiwata T.
Title Ganglioside GM2, highly expressed in the MIA PaCa-2 pancreatic ductal adenocarcinoma cell line, is correlated with growth, invasion, and advanced stage.
Journal Sci Rep
Abstract Gangliosides, a group of glycosphingolipids, are known to be cell surface markers and functional factors in several cancers. However, the association between gangliosides and pancreatic ductal adenocarcinoma (PDAC) has not been well elucidated. In this study, we examined the expression and roles of ganglioside GM2 in PDAC. GM2+ cells showed a higher growth rate than GM2- cells in the adherent condition. When GM2- and GM2+ cells were cultured three-dimensionally, almost all cells in the spheres expressed GM2, including cancer stem cell (CSC)-like cells. A glycolipid synthesis inhibitor reduced GM2 expression and TGF-β1 signaling in these CSC-like cells, presumably by inhibiting the interaction between GM2 and TGFβ RII and suppressing invasion. Furthermore, suppression of GM2 expression by MAPK inhibition also reduced TGF-β1 signaling and suppressed invasion. GM2+ cells formed larger subcutaneous tumors at a high incidence in nude mice than did GM2- cells. In PDAC cases, GM2 expression was significantly associated with younger age, larger tumor size, advanced stage and higher histological grade. These findings suggest that GM2 could be used as a novel diagnostic and therapeutic target for PDAC.
Volume 9(1)
Pages 19369
Published 2019-12-18
DOI 10.1038/s41598-019-55867-4
PII 10.1038/s41598-019-55867-4
PMID 31852956
PMC PMC6920443
MeSH Adenocarcinoma / genetics* Adenocarcinoma / pathology Aged Animals Carcinoma, Pancreatic Ductal / genetics* Carcinoma, Pancreatic Ductal / pathology Cell Line, Tumor Cell Proliferation / genetics Female G(M2) Ganglioside / genetics* Gene Expression Regulation, Neoplastic / genetics Heterografts Humans Male Mice Middle Aged Neoplasm Invasiveness / genetics Neoplasm Invasiveness / pathology Neoplastic Stem Cells / metabolism Signal Transduction Transforming Growth Factor beta1 / genetics*
IF 3.998
Times Cited 0
Human and Animal Cells PK-45P(RCB2141) PK-8(RCB2700) T3M-4(RCB1021)