Cancer Lipid Metabolism Confers Antiangiogenic Drug Resistance

Iwamoto, Hideki; Abe, Mitsuhiko; Yang, Yunlong; Cui, Dongmei; Seki, Takahiro; Nakamura, Masaki; Hosaka, Kayoko; Lim, Sharon; Wu, Jing‐Ming; He, Xingkang; Sun, Xiaoting; Lu, Yongtian; Zhou, Qingjun; Shi, Weiyun; Torimura, Takuji; Nie, Guohui; Li, Qi; Cao, Yihai

doi:10.1016/j.cmet.2018.05.005

Cited by 224 publications

(191 citation statements)

References 42 publications

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“…However, a direct effect of iDGAT on tumor cells could not be excluded. Studies reported a potent role of lipid metabolism in the survival and drug resistance of cancer cells (Boroughs & DeBerardinis, ; Iwamoto et al , ). Thus, to specifically disrupt LD formation in myeloid cells in vivo , peptide modified liposomes served as delivery vehicle for iDGAT treatment () (Karathanasis et al , ).…”

Section: Resultsmentioning

confidence: 99%

Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages

et al. 2019

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Tumor‐associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs is controlled by long‐chain fatty acid metabolism, specifically unsaturated fatty acids, here exemplified by oleate. Consequently, en‐route enriched lipid droplets were identified as essential organelles, which represent effective targets for chemical inhibitors to block in vitro polarization of TAMs and tumor growth in vivo. In line, analysis of human tumors revealed that myeloid cells infiltrating colon cancer but not gastric cancer tissue indeed accumulate lipid droplets. Mechanistically, our data indicate that oleate‐induced polarization of myeloid cells depends on the mammalian target of the rapamycin pathway. Thus, our findings reveal an alternative therapeutic strategy by targeting the pro‐tumoral myeloid cells on a metabolic level.

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Section: Resultsmentioning

confidence: 99%

Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages

et al. 2019

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“…Due to the abundance and close proximity of mammary adipose tissue (source of FAs) to breast cancer tumors, breast tumors rely on lipid metabolism to favor survival by increasing the expression of various proteins regulating lipid metabolism (68,69). This is evident by an upregulation of various enzymes catalyzing de novo FA synthesis in breast cancer cells i.e., Acetyl-CoA carboxylase (ACC), FAS and SCD-1 (13,70,71).…”

Section: Diet-induced Obesity Distinctly Alters Lipid Metabolism In Tmentioning

confidence: 99%

Decreased Efficacy of Doxorubicin Corresponds With Modifications in Lipid Metabolism Markers and Fatty Acid Profiles in Breast Tumors From Obese vs. Lean Mice

et al. 2020

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Breast cancer cells modulate lipid and fatty acid metabolism to sustain proliferation. The role of adipocytes in cancer treatment efficacy remains, however, to be fully elucidated. We investigated whether diet-induced obesity (DIO) affects the efficacy of doxorubicin treatment in a breast tumor-bearing mouse model. Female C57BL6 mice were fed a high fat or low fat diet for the full duration of the study (12 weeks). After 8 weeks, mice were inoculated with E0771 triple-negative breast cancer cells in the fourth mammary gland to develop breast tumor allographs. Tumor-bearing mice received either vehicle (Hank's balanced salt solution) or doxorubicin (chemotherapy). Plasma inflammatory markers, tumor, and mammary adipose tissue fatty acid composition, as well as protein expression of lipid metabolism markers were determined. The high fat diet (HFD) attenuated the treatment efficacy of doxorubicin. Both leptin and resistin concentrations were significantly increased in the HFD group treated with doxorubicin. Suppressed lipogenesis (decreased stearoyl CoA-desaturase-1) and lipolysis (decreased hormone-sensitive lipase) were observed in mammary adipose tissue of the DIO animals, whereas increased expression was observed in the tumor tissue of doxorubicin treated HFD mice. Obesogenic conditions induced altered tissue fatty acid (FA) compositions, which reduced doxorubicin's treatment efficacy. In mammary adipose tissue breast cancer cells suppressed the storage of FAs, thereby increasing the availability of free FAs and favored inflammation under obesogenic conditions.

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“…One example for this concept was demonstrated by a study showing that provision of lipids from the surrounding tissue blocks the effect of anti-angiogenic therapy on the growth of colorectal cancer cells (Iwamoto et al, 2018). In this system, high-fat-diet-induced liver steatosis augmented the protective effect, suggesting that diet can modulate therapeutic efficacy.…”

Section: You Are What You Eat: the Effect Of Diet On Cancer Cell Metamentioning

confidence: 99%

The big picture: exploring the metabolic cross-talk in cancer

Schulze

Yuneva

2018

Disease Models &Amp; Mechanisms

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Metabolic reprogramming is now well established as one of the hallmarks of cancer. The renewed interest in this topic has spurred a remarkable advance in our understanding of the metabolic alterations in cancer cells and in the tumour microenvironment. Initially, this research focussed on identifying the metabolic processes that provided cancer cells with building blocks for growth or to prevent oxidative damage and death. In addition to providing detailed insight into the mechanisms by which oncogenic signalling pathways modulate metabolic processes, this research also revealed multiple nodes within the metabolic network that can be targeted for the selective elimination of cancer cells. However, recent years have seen a paradigm shift in the field of cancer metabolism; while early studies focussed mainly on the metabolic processes within a cancer cell, recent approaches also consider the impact of metabolic cross-talk between different cell types within the tumour or study cancer within the organismal metabolic context. The Review articles presented in this themed Special Collection of Disease Models & Mechanisms aim to provide an overview of the recent advances in the field. The Collection also contains research articles that describe how metabolic inhibition can improve the efficacy of targeted therapy and introduce a new zebrafish model to study metabolic tumour-host interactions. We also present ‘A model for life’ interviews: a new interview with and a previously published one with that provide insight into these two leaders' personal scientific journeys that resulted in seminal discoveries in the field of cancer metabolism. In this Editorial, we summarise some of the key insights obtained from studying cancer metabolism. We also describe some of the many exciting developments in the field and discuss its future challenges.

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Cancer Lipid Metabolism Confers Antiangiogenic Drug Resistance

Cited by 224 publications

References 42 publications

Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages

Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages

Decreased Efficacy of Doxorubicin Corresponds With Modifications in Lipid Metabolism Markers and Fatty Acid Profiles in Breast Tumors From Obese vs. Lean Mice

The big picture: exploring the metabolic cross-talk in cancer

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