The peritumoural adipose tissue microenvironment and cancer. The roles of fatty acid binding protein 4 and fatty acid binding protein 5

Guaita‐Esteruelas, Sandra; Gumà, Josep; Masana, Luís; Borrás, Joan

doi:10.1016/j.mce.2017.02.002

Cited by 94 publications

(93 citation statements)

References 143 publications

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“…FABP4 is a low molecular weight protein that transports long‐chain fatty acids released from adipocytes and macrophages and can exert its metabolic action in a paracrine or exocrine manner. It is also implicated in tumorigenesis in different cancer types, including breast, prostate and ovarian cancer, and may have an active role in the interaction between tumor and AT . In fact, FABP4 is involved in lipid transfer between adipocytes and ovaric tumor cells, inducing the fatty acid oxidation pathway to fuel tumor growth .…”

Section: Discussionmentioning

confidence: 99%

“…It is also implicated in tumorigenesis in different cancer types, including breast, prostate and ovarian cancer, and may have an active role in the interaction between tumor and AT. 32 In fact, FABP4 is involved in lipid transfer between adipocytes and ovaric tumor cells, inducing the fatty acid oxidation pathway to fuel tumor growth. 36 In addition, in breast cancer, the expression of FABP4 and other adipogenesisrelated genes, were downregulated in AT adjacent to malignant breast tumors.…”

Section: Discussionmentioning

confidence: 99%

“…(Fatty Acid Binding Protein 4), involved in fatty acid uptake, transport and metabolism 32 ; and the pro-inflammatory cytokine IL-6 ( Fig. 4f ).…”

Section: Addition Hfd Increased the Expression Of Other Genes: Fabp4mentioning

confidence: 99%

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CTBP1/CYP19A1/estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome

Massillo

Dalton

Porretti

et al. 2018

Intl Journal of Cancer

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Metabolic syndrome (MeS) increases prostate cancer (PCa) risk and aggressiveness. C-terminal binding protein 1 (CTBP1) is a transcriptional co-repressor of tumor suppressor genes that is activated by low NAD /NADH ratio. Previously, our group established a MeS and PCa mice model that identified CTBP1 as a novel link associating both diseases. We found that CTBP1 controls the transcription of aromatase (CYP19A1), a key enzyme that converts androgens to estrogens. The aim of this work was to investigate the mechanism that explains CTBP1 as a link between MeS and PCa based on CYP19A1 and estrogen synthesis regulation using PCa cell lines, MeS/PCa mice and adipose co-culture systems. We found that CTBP1 and E1A binding protein p300 (EP300) bind to CYP19A1 promoter and downregulate its expression in PC3 cells. Estradiol, through estrogen receptor beta, released CTBP1 from CYP19A1 promoter triggering its transcription and modulating PCa cell proliferation. We generated NSG and C57BL/6J MeS mice by chronically feeding animals with high fat diet. In the NSG model, CTBP1 depleted PCa xenografts showed an increase in CYP19A1 expression with subsequent increment in intratumor estradiol concentrations. Additionally, in C57BL/6J mice, MeS induced hypertrophy, hyperplasia and inflammation of the white adipose tissue, which leads to a proinflammatory phenotype and increased serum estradiol concentration. Thus, MeS increased PCa growth and Ctbp1, Fabp4 and IL-6 expression levels. These results describe, for the first time, a novel CTBP1/CYP19A1/Estradiol axis that explains, in part, the mechanism for prostate tumor growth increase by MeS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CTBP1/CYP19A1/estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome

Massillo

Dalton

Porretti

et al. 2018

Intl Journal of Cancer

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show abstract

“…FABP4, the adipocyte fatty acid binding protein (A‐FABP) is involved in fatty acid trafficking and storage, and carries unesterified FAs from the cell membrane into different cellular organelles . It is involved in glucose and lipid metabolism, signal transduction, and apoptosis in both normal and cancerous (eg, prostate and breast cancer) cells . Interestingly, endogenous FABP4 is functionally responsible for aggressive patterns of disease that likely contribute to poor prognosis in ovarian cancer, and exogenous FABP4 has also been found to be involved in prostate cancer development and progression .…”

Section: Multiple Myeloma and Fatty Acid Metabolismmentioning

confidence: 99%

Multiple Myeloma and Fatty Acid Metabolism

et al. 2019

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Multiple myeloma (MM) accounts for 13% to 15% of all blood cancers and is characterized by the proliferation of malignant cells within the bone marrow (BM). Despite important advances in treatment, most patients become refractory and relapse with the disease. As MM tumors grow in the BM, they disrupt hematopoiesis, create monoclonal protein spikes in the blood, initiate systemic organ and immune system shutdown, and induce painful osteolytic lesions caused by overactive osteoclasts and inhibited osteoblasts. MM cells are also extremely dependent on the BM niche, and targeting the BM niche has been clinically transformative for inhibiting the positive‐feedback “vicious cycle” between MM cells and osteoclasts that leads to bone resorption and tumor proliferation. Bone marrow adipocytes (BMAs) are dynamic, secretory cells that have complex effects on osteoblasts and tumor cells, but their role in modifying the MM cell phenotype is relatively unexplored. Given their active endocrine function, capacity for direct cell–cell communication, correlation with aging and obesity (both MM risk factors), potential roles in bone disease, and physical proximity to MM cells, it appears that BMAs support MM cells. This supposition is based on research from many laboratories, including our own. Therapeutically targeting the BMA may prove to be equally transformative in the clinic if the pathways through which BMAs affect MM cells can be determined. In this review, we discuss the potential for BMAs to provide free fatty acids to myeloma cells to support their growth and evolution. We highlight certain proteins in MM cells responsible for fatty acid uptake and oxidation and discuss the potential for therapeutically targeting fatty acid metabolism or BMAs from where they may be derived. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

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“…Also the increase in the levels of fatty acid-binding proteins (FABP)—a family of protein involved in transporting free fatty acid—in several cancers like breast, prostate, ovarian, and colorectal carcinoma [reviewed in Ref. (250)] indicate the existence of an active sequestering of fatty acid occurring between the tumor cells and CAAs. An import of free fatty acids molecules to tumor cells has been reported in several types of cancers including ovarian and prostate carcinomas (245, 251).…”

Section: Metabolic Cooperation and Competition In The Tmementioning

confidence: 99%

Metabolic Cooperation and Competition in the Tumor Microenvironment: Implications for Therapy

2017

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The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising fibroblasts, cells of the immune system, and endothelial cells, besides various soluble secretory factors from all cellular components (including tumor cells). The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming of the metabolism occurs in tumor and non-tumor cells that underlies the nature of interactions as well as competitions ensuring steady supply of nutrients and anapleoretic molecules for the tumor cells that fuels its growth even under hypoxic conditions. This metabolic reprogramming also plays a significant role in suppressing the immune attack on the tumor cells and in resistance to therapies. Thus, the metabolic cooperation and competition among the different TME components besides the inherent alterations in the tumor cells arising out of genetic as well as epigenetic changes supports growth, metastasis, and therapeutic resistance. This review focuses on the metabolic remodeling achieved through an active cooperation and competition among the three principal components of the TME—the tumor cells, the T cells, and the cancer-associated fibroblasts while discussing about the current strategies that target metabolism of TME components. Further, we will also consider the probable therapeutic opportunities targeting the various metabolic pathways as well as the signaling molecules/transcription factors regulating them for the development of novel treatment strategies for cancer.

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The peritumoural adipose tissue microenvironment and cancer. The roles of fatty acid binding protein 4 and fatty acid binding protein 5

Cited by 94 publications

References 143 publications

CTBP1/CYP19A1/estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome

CTBP1/CYP19A1/estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome

Multiple Myeloma and Fatty Acid Metabolism

Metabolic Cooperation and Competition in the Tumor Microenvironment: Implications for Therapy

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