Is there an association between enhanced choline and β-catenin pathway in breast cancer? A pilot study by MR Spectroscopy and ELISA

Agarwal, Khushbu; Hariprasad, Gururao; Rani, Komal; Sharma, Uma; Mathur, Sandeep; Seenu, V.; Parshad, Rajinder; Jagannathan, Naranamangalam R.

doi:10.1038/s41598-017-01459-z

Cited by 7 publications

(14 citation statements)

References 67 publications

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“…Figure shows schematic diagrams of Wnt‐mediated β‐catenin pathways in normal and malignant breast tissues . In normal tissue, Wnt signaling is inactive and β‐catenin (a cellular adhesion protein) is maintained at low levels in the cytoplasm owing to its degradation via the ubiquitin‐proteasome pathway.…”

Section: In Vivo Mrs Methods In the Study Of Breast Cancer Metabolismmentioning

confidence: 99%

“…PCho increases in the cell cytosol, thereby increasing the tCho levels. An increased cytosolic β‐catenin level also increases the activity of PLD (reprinted from Reference with permission from Springer Nature)…”

Section: In Vivo Mrs Methods In the Study Of Breast Cancer Metabolismmentioning

confidence: 99%

“…However, the mechanism for aberrant activation of these pathways and the connection between them in breast cancer has not been fully understood. Therefore we undertook a study using in vivo 1 H MRS and enzyme‐linked immunosorbent assay (ELISA) to explore the molecular mechanisms related to the increased level of tCho in breast cancer patients and its association with β‐catenin and cyclin D1 . Breast tissue fractions from 20 malignant, 10 benign and 20 non‐involved breast tissues of patients were isolated.…”

Section: In Vivo Mrs Methods In the Study Of Breast Cancer Metabolismmentioning

confidence: 99%

“…Box plots showing differences in cytosolic (A, C) and nuclear (B, D) β‐catenin expression (pg/mL) and cyclin D1 expression (ng/mL) among malignant, benign and normal healthy breast tissues obtained using ELISA. **Significance with p < 0.01; * p < 0.05 (reprinted from Reference with permission from Springer Nature)…”

Section: In Vivo Mrs Methods In the Study Of Breast Cancer Metabolismmentioning

confidence: 99%

“…Dot plot representation of the difference in cytosolic β‐catenin expression (pg/mL) of PR+ and PR− breast tumors obtained using ELISA. *Significance with p < 0.05 (reprinted from Reference with permission from Springer Nature)…”

Section: In Vivo Mrs Methods In the Study Of Breast Cancer Metabolismmentioning

confidence: 99%

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Application of in vivo MR methods in the study of breast cancer metabolism

Jagannathan

2018

NMR in Biomedicine

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In the last two decades, various in vivo MR methodologies have been evaluated for their potential in the study of cancer metabolism. During malignant transformation, metabolic alterations occur, leading to morphological and functional changes. Among various MR methods, in vivo MRS has been extensively used in breast cancer to study the metabolism of cells, tissues or whole organs. It provides biochemical information at the metabolite level. Altered choline, phospholipid and energy metabolism has been documented using proton ( 1 H), phosphorus ( 31 P) and carbon ( 13 C) isotopes. Increased levels of choline-containing compounds, phosphomonoesters and phosphodiesters in breast cancer, which are indicative of altered choline and phospholipid metabolism, have been reported using in vivo, in vitro and ex vivo NMR studies. These changes are reversed on successful therapy, which depends on the treatment regimen given.Monitoring the various tumor intermediary metabolic pathways using nuclear spin hyperpolarization of 13 C-labeled substrates by dynamic nuclear polarization has also been recently reported. Furthermore, the utility of various methods such as diffusion, dynamic contrast and perfusion MRI have also been evaluated to study breast tumor metabolism. Parameters such as tumor volume, apparent diffusion coefficient, volume transfer coefficient and extracellular volume ratio are estimated. These parameters provide information on the changes in tumor microstructure, microenvironment, abnormal vasculature, permeability and grade of the tumor. Such changes seen during cancer progression are due to alterations in the tumor metabolism, leading to changes in cell architecture. Due to architectural changes, the tissue mechanical properties are altered; this can be studied using magnetic resonance elastography, which measures the elastic properties of tissues. Moreover, these structural MRI methods can be used to investigate the effect of therapy-induced changes in tumor characteristics. This review discusses the potential of various in vivo MR methodologies in the study of breast cancer metabolism.

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Section: In Vivo Mrs Methods In the Study Of Breast Cancer Metabolismmentioning

confidence: 99%

Section: In Vivo Mrs Methods In the Study Of Breast Cancer Metabolismmentioning

confidence: 99%

Section: In Vivo Mrs Methods In the Study Of Breast Cancer Metabolismmentioning

confidence: 99%

Section: In Vivo Mrs Methods In the Study Of Breast Cancer Metabolismmentioning

confidence: 99%

Section: In Vivo Mrs Methods In the Study Of Breast Cancer Metabolismmentioning

confidence: 99%

See 3 more Smart Citations

Application of in vivo MR methods in the study of breast cancer metabolism

Jagannathan

2018

NMR in Biomedicine

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MR spectroscopy in breast cancer metabolomics

Sharma

Jagannathan

2021

Analytical Science Advances

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Breast cancer poses a significant health care challenge worldwide requiring early detection and effective treatment strategies for better patient outcome. A deeper understanding of the breast cancer biology and metabolism may help developing better diagnostic and therapeutic approaches. Metabolomic studies give a comprehensive analysis of small molecule metabolites present in human tissues in vivo. The changes in the level of these metabolites provide information on the complex mechanism of the development of the disease and its progression. Metabolomic approach using analytical techniques such as magnetic resonance spectroscopy (MRS) has evolved as an important tool for identifying clinically relevant metabolic biomarkers. The metabolic characterization of breast lesions using in-vivo MRS has shown that malignant breast tissues contain elevated levels of choline containing compounds (tCho), suggesting rapid proliferation of cancer cells and alterations in membrane metabolism. Also, tCho has been identified as one of the important biomarkers that help to enhance the diagnostic accuracy of dynamic contrast enhanced magnetic resonance imaging and also for monitoring treatment response. Further, metabolome of malignant tissues can be studied using ex vivo and in vitro MRS at high magnetic fields. This provided the advantage of detection of a large number of compounds that facilitated more comprehensive insight into the altered metabolic pathways associated with the cancer development and progression and also in identification of several metabolites as potential biomarkers. This article briefly reviews the role of MRS based metabolic profiling in the discovery of biomarkers and understanding of the altered metabolism in breast cancer. K E Y W O R D Sbiomarker, breast cancer, ex vivo, in vitro, in vivo, in vivo magnetic resonance spectroscopy (MRS), metabolomics, therapeutic response INTRODUCTIONBreast cancer is a major healthcare concern for women globally. 1 Early diagnosis of breast cancer plays an important role in effective therapeutic management and in improving survival and quality-of-life. The radiological imaging techniques such as mammography and ultrasoundThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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