Inhibition of glutamate regulated calcium entry into leukemic megakaryoblasts reduces cell proliferation and supports differentiation
Tania Kamal, Taryn N Green, Marie-Christine Morel-Kopp, Christopher M Ward, Ailsa L McGregor, Susan R McGlashan, Stefan K Bohlander, Peter J Browett, Lochie Teague, Matthew J During, Timothy M Skerry, Emma C Josefsson, Maggie L Kalev-Zylinska
CELLULAR SIGNALLING | ELSEVIER SCIENCE INC | Published : 2015
Human megakaryocytes release glutamate and express glutamate-gated Ca(2+)-permeable N-methyl-D-aspartate receptors (NMDARs) that support megakaryocytic maturation. While deregulated glutamate pathways impact oncogenicity in some cancers, the role of glutamate and NMDARs in megakaryocytic malignancies remains unknown. The aim of this study was to determine if NMDARs participate in Ca(2+) responses in leukemic megakaryoblasts and if so, whether modulating NMDAR activity could influence cell growth. Three human cell lines, Meg-01, Set-2 and K-562 were used as models of leukemic megakaryoblasts. NMDAR components were examined in leukemic cells and human bone marrow, including in megakaryocytic d..View full abstract
Awarded by Child Cancer Foundation
Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
This work was funded by the Child Cancer Foundation (project 12/17) and the School of Medicine N M McBeath Child Cancer Research Fund (M-FMH-NMMCCR). T. Kamal receives Doctoral Scholarships from Anne and David Norman and the University of Auckland. Funding sources had no involvement in the study design; collection, analysis and interpretation of data; writing of the report; or the decision to submit the article for publication. Meg-01 and Set-2 cells were a kind gift from Dr. David Ritchie (Peter MacCallum Cancer Centre, Melbourne, Australia). Jacqui Ross (Biomedical Imaging Research Unit) helped with Ca<SUP>2+</SUP> flux, and Nicola Langley and Stephen Edgar (Molecular Medicine and Pathology) with flow cytometry. Srividya Arunachalam, Sugandha Chugh, James Hearn and Alyona Oryshchuk contributed immunohistochemistry and cytological stains. Sanger sequencing was performed by DNA Sequencing Facility at the School of Biological Sciences.