scholarly journals Kinetic Analysis of Lipid Metabolism in Live Breast Cancer Cells via Nonlinear Optical Microscopy

2019 ◽  
Author(s):  
J. Hou ◽  
N. E. Reid ◽  
B. J. Tromberg ◽  
E. O. Potma
Keyword(s):  
Breast Cancer ◽  
Lipid Metabolism ◽  
Optical Microscopy ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
Live Cells ◽  
Consumption Rates

AbstractInvestigating the behavior of breast cancer cells via reaction kinetics may help unravel the mechanisms that underlie metabolic changes in tumors. However, obtaining human in vivo kinetic data is challenging due to difficulties associated with measuring these parameters. Non-destructive methods of measuring lipid content in live cells, provide a novel approach to quantitatively model lipid synthesis and consumption. In this study, two-photon excited fluorescence (TPEF) was used to determine metabolic rates via the cell’s optical redox ratio (ORR) as reported by fluorescence intensity ratios of metabolic coenzymes, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD+). Concurrently, coherent Raman scattering (CRS) microscopy was used to probe de novo intracellular lipid content. Combining non-linear optical microscopy and Michaelis-Menten-kinetics based simulations, we isolated fatty acid synthesis/consumption rates and elucidated effects of altered lipid metabolism in T47D breast cancer cells. When treated with 17β-Estradiol (E2), cancer cells showed a 3-fold increase in beta-oxidation rate as well as a 50% increase in cell proliferation rate. Similarly, the rate of de novo lipid synthesis in cancer cells treated with E2 was increased by 60%. Furthermore, we treated T47D cells with etomoxir (ETO) and observed that cancer cells treated with ETO exhibited a ∼70% reduction in β-oxidation. These results show the ability to probe lipid alterations in live cells with minimum interruption, to characterize both glucose and lipid metabolism in breast cancer cells via quantitative kinetic models and parameters.Statement of SignificanceCombining non-linear optical microscopy (NLOM) and deuterium labeling provides insight into lipid metabolism in live cancer cells during cancer development and progression. The dynamic metabolic data is modelled with Michaelis-Menten-kinetics to independently quantify the lipid synthesis and utilization in cancer cells. Changes in lipid levels are found to originate from de novo lipid synthesis using glucose as a source, lipid consumption from β-oxidation and lipid consumption from cell proliferation, processes that can separately analyzed with the Michaelis-Menten model. In this work, we isolate fatty acid synthesis/consumption rates and elucidated effects of altered lipid metabolism in T47D breast cancer cells in response to estradiol stimulation and etomoxir treatment, dynamic processes that cannot be easily observed without the application of appropriate models.

scholarly journals Spot 14: A Marker of Aggressive Breast Cancer and a Potential Therapeutic Target

Endocrinology ◽  
2006 ◽  
Vol 147 (9) ◽  
pp. 4048-4055 ◽  
Author(s):  
William B. Kinlaw ◽  
Jennifer L. Quinn ◽  
Wendy A. Wells ◽  
Christopher Roser-Jones ◽  
Joel T. Moncur
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Milk Fat ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Lipid Synthesis ◽  
Breast Cancers ◽  
Spot 14 ◽  
Aggressive Breast Cancer

Spot 14 (S14) is a nuclear protein that communicates the status of dietary fuels and fuel-related hormones to genes required for long-chain fatty acid synthesis. In mammary gland, S14 is important for both epithelial proliferation and milk fat production. The S14 gene is amplified in some breast cancers and is strongly expressed in most. High expression of S14 in primary invasive breast cancer is conspicuously predictive of recurrence. S14 mediates the induction of lipogenesis by progestin in breast cancer cells and accelerates their growth. Conversely, S14 knockdown impairs de novo lipid synthesis and causes apoptosis. We found that breast cancer cells do not express lipoprotein lipase (LPL) and hypothesize that they do not have access to circulating lipids unless the local environment supplies it. This may explain why primary breast cancers with low S14 do not survive transit from the LPL-rich mammary fat pad to areas devoid of LPL, such as lymph nodes, and thus do not appear as distant metastases. Thus, S14 is a marker for aggressive breast cancer and a potential target as well. Future effort will center on validation of S14 as a therapeutic target and producing antagonists of its action.

scholarly journals Elevated Expression of DecR1 Impairs ErbB2/Neu-Induced Mammary Tumor Development

2007 ◽  
Vol 27 (18) ◽  
pp. 6361-6371 ◽  
Author(s):  
Josie Ursini-Siegel ◽  
Ashish B. Rajput ◽  
Huiling Lu ◽  
Virginie Sanguin-Gendreau ◽  
Dongmei Zuo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Mammary Tumor ◽  
Fatty Acid Synthesis ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Acid Synthesis ◽  
Mammary Tumor Cells

ABSTRACT Tumor cells utilize glucose as a primary energy source and require ongoing lipid biosynthesis for growth. Expression of DecR1, an auxiliary enzyme in the fatty acid β-oxidation pathway, is significantly diminished in numerous spontaneous mammary tumor models and in primary human breast cancer. Moreover, ectopic expression of DecR1 in ErbB2/Neu-induced mammary tumor cells is sufficient to reduce levels of ErbB2/Neu expression and impair mammary tumor outgrowth. This correlates with a decreased proliferative index and reduced rates of de novo fatty acid synthesis in DecR1-expressing breast cancer cells. Although DecR1 expression does not affect glucose uptake in ErbB2/Neu-transformed cells, sustained expression of DecR1 protects mammary tumor cells from apoptotic cell death following glucose withdrawal. Moreover, expression of catalytically impaired DecR1 mutants in Neu-transformed breast cancer cells restored Neu expression levels and increased mammary tumorigenesis in vivo. These results argue that DecR1 is sufficient to limit breast cancer cell proliferation through its ability to limit the extent of oncogene expression and reduce steady-state levels of de novo fatty acid synthesis. Furthermore, DecR1-mediated suppression of tumorigenesis can be uncoupled from its effects on Neu expression. Thus, while downregulation of Neu expression may contribute to DecR1-mediated tumor suppression in certain cell types, this is not an obligate event in all Neu-transformed breast cancer cells.

scholarly journals Glucose-sensitive acetylation of Seryl tRNA synthetase regulates lipid synthesis in breast cancer

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jin Zhao ◽  
Hangming Bai ◽  
Xiaoyu Li ◽  
Jie Yan ◽  
Gengyi Zou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
De Novo ◽  
Lipid Synthesis ◽  
Trna Synthetase ◽  
Lipid Biosynthesis ◽  
Normal Mammary Gland ◽  
Dependent Manner

AbstractAbnormally enhanced de novo lipid biosynthesis has been increasingly realized to play crucial roles in the initiation and progression of varieties of cancers including breast cancer. However, the mechanisms underlying the dysregulation of lipid biosynthesis in breast cancer remain largely unknown. Here, we reported that seryl tRNA synthetase (SerRS), a key enzyme for protein biosynthesis, could translocate into the nucleus in a glucose-dependent manner to suppress key genes involved in the de novo lipid biosynthesis. In normal mammary gland epithelial cells glucose can promote the nuclear translocation of SerRS by increasing the acetylation of SerRS at lysine 323. In SerRS knock-in mice bearing acetylation-defective lysine to arginine mutation, we observed increased body weight and adipose tissue mass. In breast cancer cells the acetylation and nuclear translocation of SerRS are greatly inhibited. Overexpression of SerRS, in particularly the acetylation-mimetic lysine to glutamine mutant, dramatically inhibits the de novo lipid synthesis and hence greatly suppresses the proliferation of breast cancer cells and the growth of breast cancer xenografts in mice. We further identified that HDAC4 and HDAC5 regulated the acetylation and nuclear translocation of SerRS. Thus, we identified a SerRS-meditated inhibitory pathway in glucose-induced lipid biosynthesis, which is dysregulated in breast cancer.

De novo expression of transfected Sirt3 enhances susceptibility of human MCF-7 breast cancer cells to hyperoxia treatment

2018 ◽  
Vol 120 ◽  
pp. S56
Author(s):  
Iva I. Podgorski ◽  
Marija Pinterić ◽  
Sandra Sobočanec ◽  
Marijana Popović Hadžija ◽  
Mladen Paradžik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Mcf 7

Abstract 3744: Differences in lipid metabolism between non-metastatic and metastatic breast cancer cells

2020 ◽  
Author(s):  
Chaylen Andolino ◽  
Josie Asher ◽  
Alyssa S. Zembroski ◽  
Kimberly Buhman ◽  
Dorothy Teegarden
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Breast

scholarly journals Breast Cancer Cells in Microgravity: New Aspects for Cancer Research

2020 ◽  
Vol 21 (19) ◽  
pp. 7345 ◽  
Author(s):  
Mohamed Zakaria Nassef ◽  
Daniela Melnik ◽  
Sascha Kopp ◽  
Jayashree Sahana ◽  
Manfred Infanger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Tumor Model ◽  
Cancer Drug ◽  
Cancer Therapies

Breast cancer is the leading cause of cancer death in females. The incidence has risen dramatically during recent decades. Dismissed as an “unsolved problem of the last century”, breast cancer still represents a health burden with no effective solution identified so far. Microgravity (µg) research might be an unusual method to combat the disease, but cancer biologists decided to harness the power of µg as an exceptional method to increase efficacy and precision of future breast cancer therapies. Numerous studies have indicated that µg has a great impact on cancer cells; by influencing proliferation, survival, and migration, it shifts breast cancer cells toward a less aggressive phenotype. In addition, through the de novo generation of tumor spheroids, µg research provides a reliable in vitro 3D tumor model for preclinical cancer drug development and to study various processes of cancer progression. In summary, µg has become an important tool in understanding and influencing breast cancer biology.

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