Search engine for discovering works of Art, research articles, and books related to Art and Culture
ShareThis
Javascript must be enabled to continue!

Abstract 1485: Measuring relative utilization of aerobic glycolysis in breast cancer cells by positional isotopic discrimination

View through CrossRef
Abstract Cancer deaths, including breast cancer, are caused by metastasis of the malignant tumors to distant locations. However, current methods of detection cannot distinguish pre-invasive breast cancer from noninvasive breast tumor or benign breast disease. Population-wide mammographic screenings have led to increased detection of ductal carcinoma in situ or DCIS, noninvasive, proliferative cells contained by the basement membrane of the terminal ductal lobular unit. DCIS is usually not associated with metastasis and/or cancer death. Each year, in the US alone, about 1.5 million of women who have been diagnosed with DCIS or a suspicious lump/lesion by mammography will require resection or breast biopsy after diagnosis for further pathologic analysis. However, ~80-85% of biopsies result in noninvasive breast disease or benign findings. As a result, a considerable number of patients suffer from side effects caused by breast biopsy and/or overtreatment. Therefore, there is an urgent need to find a biomarker for pre-invasive breast cancer. The ability of cancer cells to produce lactate through aerobic glycolysis (the Warburg effect) is a consistent hallmark of cancer, including breast cancer. Recent advancements in liquid chromatography-mass spectrometry (LC-MS) technology have significantly improved the sensitivity of this method compared to traditional NMR or GC-MS-based technologies, which make it feasible to detect very low concentrations of small molecules or metabolites. We have recently established a positional isotopic labeling and LC-MS-based targeted metabolomics method that can directly measure the conversion from [1-13C]glucose to [3-13C]lactate through glycolysis. Our results show that metastatic breast cancer cells exhibit a dramatically increased production of [3-13C]lactate from [1-13C]glucose even under aerobic conditions as compared to low- or noninvasive breast cancer cell lines. We found that the rate of aerobic glycolysis is closely correlated with glucose uptake and lactate production in breast cancer cells. We have also observed significantly elevated production of [3-13C]lactate in serum samples of early stage metastatic mammary tumors developed in mice. Since elevated levels of lactate are closely correlated to increased tumor aggressiveness, these results suggest that monitoring of lactate production from glycolysis by targeted metabolomics may provide a biomarker for pre-invasive breast cancer. These results will pave the way for further exploration of the elevated production of lactate as a promising biomarker for pre-invasive breast cancer and for assessment of therapeutic response in clinical trials. Citation Format: Da-Qing Yang, Margot Cleary. Measuring relative utilization of aerobic glycolysis in breast cancer cells by positional isotopic discrimination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1485. doi:10.1158/1538-7445.AM2017-1485
American Association for Cancer Research (AACR)
Title: Abstract 1485: Measuring relative utilization of aerobic glycolysis in breast cancer cells by positional isotopic discrimination
Description:
Abstract Cancer deaths, including breast cancer, are caused by metastasis of the malignant tumors to distant locations.
However, current methods of detection cannot distinguish pre-invasive breast cancer from noninvasive breast tumor or benign breast disease.
Population-wide mammographic screenings have led to increased detection of ductal carcinoma in situ or DCIS, noninvasive, proliferative cells contained by the basement membrane of the terminal ductal lobular unit.
DCIS is usually not associated with metastasis and/or cancer death.
Each year, in the US alone, about 1.
5 million of women who have been diagnosed with DCIS or a suspicious lump/lesion by mammography will require resection or breast biopsy after diagnosis for further pathologic analysis.
However, ~80-85% of biopsies result in noninvasive breast disease or benign findings.
As a result, a considerable number of patients suffer from side effects caused by breast biopsy and/or overtreatment.
Therefore, there is an urgent need to find a biomarker for pre-invasive breast cancer.
The ability of cancer cells to produce lactate through aerobic glycolysis (the Warburg effect) is a consistent hallmark of cancer, including breast cancer.
Recent advancements in liquid chromatography-mass spectrometry (LC-MS) technology have significantly improved the sensitivity of this method compared to traditional NMR or GC-MS-based technologies, which make it feasible to detect very low concentrations of small molecules or metabolites.
We have recently established a positional isotopic labeling and LC-MS-based targeted metabolomics method that can directly measure the conversion from [1-13C]glucose to [3-13C]lactate through glycolysis.
Our results show that metastatic breast cancer cells exhibit a dramatically increased production of [3-13C]lactate from [1-13C]glucose even under aerobic conditions as compared to low- or noninvasive breast cancer cell lines.
We found that the rate of aerobic glycolysis is closely correlated with glucose uptake and lactate production in breast cancer cells.
We have also observed significantly elevated production of [3-13C]lactate in serum samples of early stage metastatic mammary tumors developed in mice.
Since elevated levels of lactate are closely correlated to increased tumor aggressiveness, these results suggest that monitoring of lactate production from glycolysis by targeted metabolomics may provide a biomarker for pre-invasive breast cancer.
These results will pave the way for further exploration of the elevated production of lactate as a promising biomarker for pre-invasive breast cancer and for assessment of therapeutic response in clinical trials.
Citation Format: Da-Qing Yang, Margot Cleary.
Measuring relative utilization of aerobic glycolysis in breast cancer cells by positional isotopic discrimination [abstract].
In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC.
Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1485.
doi:10.
1158/1538-7445.
AM2017-1485.

Related Results

Breast Carcinoma within Fibroadenoma: A Systematic Review
Breast Carcinoma within Fibroadenoma: A Systematic Review
Abstract Introduction Fibroadenoma is the most common benign breast lesion; however, it carries a potential risk of malignant transformation. This systematic review provides an ove...
Desmoid-Type Fibromatosis of The Breast: A Case Series
Desmoid-Type Fibromatosis of The Breast: A Case Series
Abstract IntroductionDesmoid-type fibromatosis (DTF), also called aggressive fibromatosis, is a rare, benign, locally aggressive condition. Mammary DTF originates from fibroblasts ...
Abstract OI-1: OI-1 Decoding breast cancer predisposition genes
Abstract OI-1: OI-1 Decoding breast cancer predisposition genes
Abstract Women with one or more first-degree female relatives with a history of breast cancer have a two-fold increased risk of developing breast cancer. This risk i...
Spanish Breast Cancer Research Group (GEICAM)
Spanish Breast Cancer Research Group (GEICAM)
This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Spanish Breast Cancer Research Group (GEICAM). Clinical trials...
International Breast Cancer Study Group (IBCSG)
International Breast Cancer Study Group (IBCSG)
This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by International Breast Cancer Study Group (IBCSG). Clinical tria...
Abstract 173: Adipocytes-derived collagen reorganization in microenvironment promotes breast cancer progression
Abstract 173: Adipocytes-derived collagen reorganization in microenvironment promotes breast cancer progression
Abstract Purposes Breast cancer cells recruit surrounding stromal cells, such as cancer-associated fibroblasts (CAFs), to reorganize collagen and prom...
Abstract 1308: Protein profiling of breast cancer cell-derived extracellular vesicles in breast to bone metastasis
Abstract 1308: Protein profiling of breast cancer cell-derived extracellular vesicles in breast to bone metastasis
Abstract Breast cancer is the most common cancer among women worldwide, with bone being one of the most common sites for breast cancer metastasis. Despite improvemen...

Back to Top