Nm23-transfected MDA-MB-435 human breast carcinoma cells form tumors with altered phospholipid metabolism and pH: a 31P nuclear magnetic resonance study in vivo and in vitro.
Nm23 genes are involved in the control of the metastatic potential of breast carcinoma cells. To understand the impact of nm23 genes on tumor physiology and metabolism, a 31P nuclear magnetic resonance (NMR) spectroscopic study was performed on tumors formed in the mammary fat pad of severe combined immunodeficiency mice by MDA-MB-435 human breast carcinoma cells transfected with cDNA encoding wild type nm23-H1 and nm23-H2 proteins. Tumors formed by MDA-MB-435 cells transfected with vector alone were used as controls. All transgene tumors exhibited significantly higher levels of phosphodiester (PDE) compounds relative to phosphomonoester (PME) compounds in vivo compared with control tumors. Similar differences in PDE and PME also were observed for spectra obtained from cells growing in culture. Intracellular pH was significantly lower and extracellular pH was significantly higher for transgene tumors compared with control tumors. Histologic analysis of lung sections confirmed reductions in incidence, number, and size of metastatic nodules for animals bearing transgene tumors. These results suggest that nm23 genes may affect suppression of metastasis through phospholipid-mediated signaling and cellular pH regulation.
Bhujwalla
Z M
ZM
Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. zaver@mri.jhu.edu
Aboagye
E O
EO
Gillies
R J
RJ
Chacko
V P
VP
Mendola
C E
CE
Backer
J M
JM
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004983:Ethanolamines / Q000032:analysis; D005260:Female; D005822:Genetic Vectors; D005997:Glycerylphosphorylcholine / Q000032:analysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics*; D010714:Phosphatidylethanolamines / Q000032:analysis; D010743:Phospholipids / Q000235:genetics / Q000378:metabolism*; D010759:Phosphorus Isotopes; D010767:Phosphorylcholine / Q000032:analysis; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D004983:Ethanolamines; D054778:NM23 Nucleoside Diphosphate Kinases; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D010759:Phosphorus Isotopes; D014157:Transcription Factors; D010767:Phosphorylcholine; C002449:glycerophosphoethanolamine; D005997:Glycerylphosphorylcholine; C005448:phosphorylethanolamine; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins