RRC ID 54108
Author Aoshima K, Fukui Y, Gulay KCM, Erdemsurakh O, Morita A, Kobayashi A, Kimura T.
Title Notch2 signal is required for the maintenance of canine hemangiosarcoma cancer stem cell-like cells.
Journal BMC Vet Res
Abstract BACKGROUND:Hemangiosarcoma (HSA) is a malignant tumor derived from endothelial cells which usually shows poor prognosis due to its high invasiveness, metastatic rate and severe hemorrhage from tumor ruptures. Since the pathogenesis of HSA is not yet complete, further understanding of its molecular basis is required.
RESULTS:Here, we identified Notch2 signal as a key factor in maintaining canine HSA cancer stem cell (CSC)-like cells. We first cultured HSA cell lines in adherent serum-free condition and confirmed their CSC-like characteristics. Notch signal was upregulated in the CSC-like cells and Notch signal inhibition by a γ-secretase inhibitor significantly repressed their growth. Notch2, a Notch receptor, was highly expressed in the CSC-like cells. Constitutive activation of Notch2 increased clonogenicity and number of cells which were able to survive in serum-free condition. In contrast, inhibition of Notch2 activity showed opposite effects. These results suggest that Notch2 is an important factor for maintaining HSA CSC-like cells. Neoplastic cells in clinical cases also express Notch2 higher than endothelial cells in the normal blood vessels in the same slides.
CONCLUSION:This study provides foundation for further stem cell research in HSA and can provide a way to develop effective treatments to CSCs of endothelial tumors.
Volume 14(1)
Pages 301
Published 2018-10-3
DOI 10.1186/s12917-018-1624-8
PII 10.1186/s12917-018-1624-8
PMID 30285832
PMC PMC6171240
MeSH Amyloid Precursor Protein Secretases / antagonists & inhibitors Animals Cell Line, Tumor Dogs Hemangiosarcoma / drug therapy* Hemangiosarcoma / metabolism Neoplastic Stem Cells / drug effects* Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Receptor, Notch2 / antagonists & inhibitors* Receptor, Notch2 / metabolism Signal Transduction / drug effects
IF 1.792
Times Cited 1
Human and Animal Cells 293T(RCB2202)