TY - JOUR
T1 - Nuclear magnetic resonance detects phosphoinositide 3-kinase/AKT- independent traits common to pluripotent murine embryonic stem cells and their malignant counterparts
AU - Romanska, Hanna M.
AU - Tiziani, Stefano
AU - Howe, Rachael C.
AU - Günther, Ulrich L.
AU - Gulzar, Zulfiqar
AU - Lalani, El Nasir
N1 - Funding Information:
Address all correspondence to: Prof. El-Nasir Lalani, Department of Molecular and Cellular Pathology, Aga Khan University, Stadium Road, PO Box 3500, Karachi, 74800, Pakistan. E-mail: [email protected] 1The authors thank the EU for supporting S.T. through the Marie Curie Transfer of Knowledge award MOTET (MTKD-CT-2004-014434). The authors also thank the Wellcome Trust and the EU in the context of the EU-NMR grant (RII3-026145) for supporting the HWB-NMR facility in Birmingham. 2Author contribution: H.M.R. and S.T. contributed equally to the manuscript. Received 27 May 2009; Revised 10 August 2009; Accepted 10 August 2009 Copyright © 2009 Neoplasia Press, Inc. All rights reserved 1522-8002/09/$25.00 DOI 10.1593/neo.09850
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2009/12
Y1 - 2009/12
N2 - Pluripotent embryonic stem (ES) cells, a potential source of somatic precursors for cell therapies, cause tumors after transplantation. Studies of mammalian carcinogenesis using nuclear magnetic resonance (NMR) spectroscopy have revealed changes in the choline region, particularly increased phosphocholine (PCho) content. High PCho levels in murine ES (mES) cells have recently been attributed to cell pluripotency. The phosphoinositide 3-kinase (PI3K)/Akt pathway has been implicated in tumor-like properties of mES cells. This study aimed to examine a potential link between the metabolic profile associated with choline metabolism of pluripotent mES cells and PI3K/Akt signaling. We used mES (ES-D3) and murine embryonal carcinoma cells (EC-F9) and compared the metabolic profiles of 1) pluripotent mES (ESD0), 2) differentiated mES (ESD14), and 3) pluripotent F9 cells. Involvement of the PI3K/Akt pathway was assessed using LY294002, a selective PI3K inhibitor. Metabolic profiles were characterized in the extracted polar fraction by 1H NMR spectroscopy. Similarities were found between the levels of choline phospholipid metabolites (PCho/total choline and PCho/glycerophosphocholine [GPCho]) in ESD0 and F9 cell spectra and a greater-than five-fold decrease of the PCho/GPCho ratio associated with mES cell differentiation. LY294002 caused no significant change in relative PCho levels but led to a greater-than two-fold increase in PCho/GPCho ratios. These results suggest that the PCho/GPCho ratio is a metabolic trait shared by pluripotent and malignant cells and that PI3K does not underlie its development. It is likely that the signature identified here in a mouse model may be relevant for safe therapeutic applications of human ES cells.
AB - Pluripotent embryonic stem (ES) cells, a potential source of somatic precursors for cell therapies, cause tumors after transplantation. Studies of mammalian carcinogenesis using nuclear magnetic resonance (NMR) spectroscopy have revealed changes in the choline region, particularly increased phosphocholine (PCho) content. High PCho levels in murine ES (mES) cells have recently been attributed to cell pluripotency. The phosphoinositide 3-kinase (PI3K)/Akt pathway has been implicated in tumor-like properties of mES cells. This study aimed to examine a potential link between the metabolic profile associated with choline metabolism of pluripotent mES cells and PI3K/Akt signaling. We used mES (ES-D3) and murine embryonal carcinoma cells (EC-F9) and compared the metabolic profiles of 1) pluripotent mES (ESD0), 2) differentiated mES (ESD14), and 3) pluripotent F9 cells. Involvement of the PI3K/Akt pathway was assessed using LY294002, a selective PI3K inhibitor. Metabolic profiles were characterized in the extracted polar fraction by 1H NMR spectroscopy. Similarities were found between the levels of choline phospholipid metabolites (PCho/total choline and PCho/glycerophosphocholine [GPCho]) in ESD0 and F9 cell spectra and a greater-than five-fold decrease of the PCho/GPCho ratio associated with mES cell differentiation. LY294002 caused no significant change in relative PCho levels but led to a greater-than two-fold increase in PCho/GPCho ratios. These results suggest that the PCho/GPCho ratio is a metabolic trait shared by pluripotent and malignant cells and that PI3K does not underlie its development. It is likely that the signature identified here in a mouse model may be relevant for safe therapeutic applications of human ES cells.
UR - http://www.scopus.com/inward/record.url?scp=72949106484&partnerID=8YFLogxK
U2 - 10.1593/neo.09850
DO - 10.1593/neo.09850
M3 - Journal articles
AN - SCOPUS:72949106484
SN - 1522-8002
VL - 11
SP - 1301
EP - 1308
JO - Neoplasia
JF - Neoplasia
IS - 12
ER -
