Notch2 signal is required for the maintenance of canine hemangiosarcoma cancer stem cell-like cells.

Publisher: BioMed Central Country of Publication: England NLM ID: 101249759 Publication Model: Electronic Cited Medium: Internet ISSN: 1746-6148 (Electronic) Linking ISSN: 17466148 NLM ISO Abbreviation: BMC Vet Res Subsets: MEDLINE

Original Publication: London : BioMed Central, 2005-

Hemangiosarcoma/*drug therapy ; Neoplastic Stem Cells/*drug effects ; Receptor, Notch2/*antagonists & inhibitors; Amyloid Precursor Protein Secretases/antagonists & inhibitors ; Animals ; Cell Line, Tumor ; Dogs ; Hemangiosarcoma/metabolism ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Receptor, Notch2/metabolism ; Signal Transduction/drug effects

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.

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18K14575 Japan Society for the Promotion of Science

Keywords: Cancer stem cell-like cells; Hemangiosarcoma; Notch2; Oncology; Tumor Biology

0 (Receptor, Notch2)
EC 3.4.- (Amyloid Precursor Protein Secretases)

Date Created: 20181005 Date Completed: 20181108 Latest Revision: 20181114

20221213

PMC6171240

10.1186/s12917-018-1624-8

30285832