Abnormal Choline Phospholipid Metabolism in Breast and Ovary Cancer: Molecular Bases for Noninvasive Imaging Approaches
نویسندگان
چکیده
Elevated contents of choline phospholipid metabolites are typically detected by nuclear magnetic resonance spectroscopy (MRS) in human and animal tumors. An increase in the intensity of the 1 H-MRS profile of total cholinecontaining compounds (tCho, 3.2 ppm) is today considered as a common feature in different types of cancer, beyond their otherwise wide phenotypic variability. This finding fostered investigations on the molecular mechanisms underlying the observed spectral changes and on correlations between aberrant phospholipid metabolism and tumor progression. At the clinical level, efforts are addressed to evaluate effectiveness and potential use of in vivo localized MRS and choline-based positron emission tomography (Cho-PET) in cancer diagnosis. Aims of this article are: a) to overview recent advances in the identification of biochemical pathways responsible for the altered 1 H-MRS tCho profile in breast and ovary cancer cells, as a basis for interpreting in vivo MR spectra and enhanced uptake of radiolabeled choline in PET; b) to summarize recent developments of in vivo 1 H-MRS methods in breast cancer diagnosis; c) to discuss the potentialities of complementing current diagnostic modalities with noninvasive MRS and Cho-PET methods to monitor biochemical alterations associated with progression, relapse and therapy response in ovary cancer.
منابع مشابه
Choline phospholipid metabolism in human ovarian tumor progression: a MRS study
INTRODUCTION Epithelial ovarian cancer (EOC) is the gynecologic neoplasia with the highest death rate, partly because of limited understanding of its patho-physiology mechanisms. Early diagnosis of EOC is critically important in disease prognosis and patient survival. Non-invasive detection of response to treatment and relapse are crucial to improve patient management. Detection by MRS of abnor...
متن کاملRNA interference-mediated choline kinase suppression in breast cancer cells induces differentiation and reduces proliferation.
Choline kinase is overexpressed in breast cancer cells and activated by oncogenes and mitogenic signals, making it a potential target for cancer therapy. Here, we have examined, for the first time, the effects of RNA interference (RNAi)-mediated down-regulation of choline kinase in nonmalignant and malignant human breast epithelial cell lines using magnetic resonance spectroscopy (MRS) as well ...
متن کاملMolecular Effects of Doxorubicin on Choline Metabolism in Breast Cancer12
Abnormal choline phospholipid metabolism is a hallmark of cancer. The magnetic resonance spectroscopy (MRS) detected total choline (tCho) signal can serve as an early noninvasive imaging biomarker of chemotherapy response in breast cancer. We have quantified the individual components of the tCho signal, glycerophosphocholine (GPC), phosphocholine (PC) and free choline (Cho), before and after tr...
متن کاملAlterations of choline phospholipid metabolism in ovarian tumor progression.
Recent characterization of abnormal phosphatidylcholine metabolism in tumor cells by nuclear magnetic resonance (NMR) has identified novel fingerprints of tumor progression that are potentially useful as clinical diagnostic indicators. In the present study, we analyzed the concentrations of phosphatidylcholine metabolites, activities of phosphocholine-producing enzymes, and uptake of [methyl-14...
متن کاملTargeting Phospholipid Metabolism in Cancer
All cancers tested so far display abnormal choline and ethanolamine phospholipid metabolism, which has been detected with numerous magnetic resonance spectroscopy (MRS) approaches in cells, animal models of cancer, as well as the tumors of cancer patients. Since the discovery of this metabolic hallmark of cancer, many studies have been performed to elucidate the molecular origins of deregulated...
متن کامل