Silencing of the glycerophosphocholine phosphodiesterase GDPD5 alters the phospholipid metabolite profile in a breast cancer model in vivo as monitored by (31) P MRS.
Abnormal choline phospholipid metabolism is an emerging hallmark of cancer, which is implicated in carcinogenesis and tumor progression. The malignant metabolic phenotype is characterized by high levels of phosphocholine (PC) and relatively low levels of glycerophosphocholine (GPC) in aggressive breast cancer cells. Phosphorus ((31) P) MRS is able to non-invasively detect these water-soluble metabolites of choline as well as ethanolamine phospholipid metabolism. Here we have investigated the effects of stably silencing glycerophosphoester diesterase domain containing 5 (GDPD5), which is an enzyme with glycerophosphocholine phosphodiesterase activity, in MDA-MB-231 breast cancer cells and orthotopic tumor xenografts. Tumors in which GDPD5 was stably silenced with GDPD5-specific shRNA contained increased levels of GPC and phosphoethanolamine (PE) compared with control tumors.
The Johns Hopkins University In vivo Cellular and Molecular Imaging Center, Division of Cancer Imaging Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
J P
JP
Wijnen
L
L
Jiang
T R
TR
Greenwood
M
M
Cheng
M
M
Döpkens
M D
MD
Cao
Z M
ZM
Bhujwalla
B
B
Krishnamachary
D W J
DW
Klomp
K
K
Glunde
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D010743:Phospholipids / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000502:physiology*; D010759:Phosphorus Isotopes
D010743:Phospholipids; D010759:Phosphorus Isotopes; D010727:Phosphoric Diester Hydrolases; C020677:glycerophosphocholine phosphodiesterase
31P MRS; GDPD5; breast cancer; glycerophosphoesterdiesterase; in vivo; metabolism; silencing