Phosphocholine as a biomarker of breast cancer: Molecular and biochemical studies

Abstract

The discovery of metabolic and molecular markers that help improving the detection and diagnosis of breast cancer is an important goal to be achieved. A high composite-choline signal in magnetic resonance spectra of breast lesions has been demonstrated to improve the accuracy of breast cancer diagnosis. In the present study we revealed the principal molecular and biochemical steps associated with the induction of choline metabolism and phosphocholine accumulation in human breast cancer cell-lines in comparison with normal human mammary epithelial cells. We found upregulation of the expression levels of specific choline transporters: organic cation transporter-2 and choline high affinity transporter-1, as well as of the enzyme choline kinase a in the cancerous cells in comparison with that in the normal mammary epithelial cells. The expression levels of choline transporter like-1, organic cation transporter-1 and choline kinase b were similar in normal and cancerous cells. We further showed that choline transport rates and choline kinase activity indeed increased by several fold in the cancer cells leading to the elevation of phosphocholine. The results strongly suggest that phosphocholine can serve as a biomarker of breast cancer reflecting upregulation of specific choline transporters and choline kinase genes. ' 2007 Wiley-Liss, Inc.

Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis

“…3C), suggesting disruptions to metabolic pathways downstream of EDI3. Previous studies have shown that the activity of CK, which generates PC from choline, is increased in cancer cells (4,7,(10)(11)(12). EDI3 acts upstream of CK, adding further evidence that disruption of this metabolic pathway can play a significant role in tumor progression.…”

“…Targeting CK with inhibitors resulted in antimitogenic and antiproliferative effects (13). It has also been reported that an increased rate of choline transport may be responsible for the increased PC levels (10,14,15). However, gene-expression analysis of members of the three choline transporter families in ovarian cancer cells showed no differential levels for the high-affinity transporter families compared with normal cells (7).…”

“…Choline kinase (CK) is the enzyme responsible for the phosphorylation of available intracellular choline to PC, and is active in malignant cells and tumors of lung, colon, breast, cervix, and ovary (4,7,(10)(11)(12). Targeting CK with inhibitors resulted in antimitogenic and antiproliferative effects (13).…”

EDI3 links choline metabolism to integrin expression, cell adhesion and spreading

“…[6][7][8][9][10] With respect to the latter, recent studies have suggested that elevated choline metabolism, including increased phosphocholine (PC) levels, is associated with worse prognosis. 9,[11][12][13] However, the mechanism of how higher PC levels contribute to cancer progression is not fully understood.…”

Microfluidic sampling system for tissue analytics

“…3 An amount of different phospholipids has been studied as biomarkers for ovarian 4 and breast cancers. 5 The role of metabolites and lipids such as Phosphatidylcholines (PCs) and Phosphoethanolamines (PEs) as breast cancer biomarkers has been investigated by Eliyahu et al, 6 Hilvo et al, 7 and Butczies et al 8 Separation of breast cancer tissues from normal breast tissues was demonstrated to be feasible with high sensitivity and specificity. The same PC and PE biomarkers were also detected from urine samples by Kim et al 9 They succeeded to measure PC and PE lipids with nanoflow liquid chromatography tandem mass spectrometry.…”