Fatty Acid Mediators in the Tumor Microenvironment

Khadge, Saraswoti; Sharp, John; Thiele, Geoffrey M.; McGuire, Timothy R.; Talmadge, James E.

doi:10.1007/978-3-030-43093-1_8

Cited by 11 publications

(8 citation statements)

References 262 publications

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“…Moreover, they are involved in cell signaling as precursors of biological active mediators. The bioactive lipid molecules are produced by the activation of multiple signaling pathways and, in cancer, might regulate multiple cellular effects [4][5][6]. Fatty acids (FA), glycerophospholipids (PL), sphingolipids (SL), and sterols, in particular, cholesterol peroxidase (HRP)-linked antibody, purchased from Cell Signaling Technology, Danvers, MA, USA.…”

Section: Introductionmentioning

confidence: 99%

Exogenous Fatty Acids Modulate ER Lipid Composition and Metabolism in Breast Cancer Cells

Rizzo¹,

Colombo²,

Montorfano³

et al. 2021

Cells

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(1) Background: Lipid metabolism is a fundamental hallmark of all tumors, especially of breast cancer. Few studies describe the different lipid metabolisms and sensitivities to the microenvironment of breast cancer cell subtypes that influence the proliferation, aggressiveness, and success of therapy. This study describes the impact of lipid microenvironment on endoplasmic reticulum (ER) membrane and metabolic activity in two breast cancer cell lines with Luminal A and triple-negative breast cancer (TNBC) features. (2) Methods: We investigated the peculiar lipid phenotype of a TNBC cell line, MDA-MB-231, and a Luminal A cell line, MCF7, and their different sensitivity to exogenous fatty acids (i.e., palmitic acid (PA) and docosahexaenoic acid (DHA)). Moreover, we verified the impact of exogenous fatty acids on ER lipid composition. (3) Results: The data obtained demonstrate that MDA-MB-231 cells are more sensitive to the lipid microenvironment and that both PA and DHA are able to remodel their ER membranes with consequences on resident enzyme activity. On the contrary, MCF7 cells are less sensitive to PA, whereas they incorporate DHA, although less efficiently than MDA-MB-231 cells. (4) Conclusions: This study sustains the importance of lipid metabolism as an innovative hallmark to discriminate breast cancer subclasses and to develop personalized and innovative pharmacological strategies. The different sensitivities to the lipid environment shown by MCF7 and MDA-MB-231 cells might be related to cell malignancy and chemoresistance onset. In the future, this new approach could lead to a substantial decrease both in deleterious side effects for the patients and in the cost of entire therapeutic treatments coupled with increased therapy efficiency.

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Section: Introductionmentioning

confidence: 99%

Exogenous Fatty Acids Modulate ER Lipid Composition and Metabolism in Breast Cancer Cells

Rizzo¹,

Colombo²,

Montorfano³

et al. 2021

Cells

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“… 37 , 38 Notably, it has been hypothesized that one of the mechanisms by which obesity promotes cancer mortality is through the induction of MDSCs. 39 – 41 In accordance with this hypothesis, obese mice with renal cancer develop a robust immunosuppressive environment that is characterized by heightened local and systemic CCR2 + MDSC prevalence. 42 In a pancreatic cancer mouse model of diet-induced obesity, cells expressing common neutrophil and MDSC markers (Gr1 + CD11b + ) were recruited to the pancreas by adipocytes and pancreatic stellate cells producing the pro-inflammatory mediator IL-1β.…”

Section: Interconnection Between Metabolic Syndrome and Inflammationmentioning

confidence: 73%

Implications of metabolism-driven myeloid dysfunctions in cancer therapy

et al. 2020

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Immune homeostasis is maintained by an adequate balance of myeloid and lymphoid responses. In chronic inflammatory states, including cancer, this balance is lost due to dramatic expansion of myeloid progenitors that fail to mature to functional inflammatory neutrophils, macrophages, and dendritic cells (DCs), thus giving rise to a decline in the antitumor effector lymphoid response. Cancer-related inflammation orchestrates the production of hematopoietic growth factors and cytokines that perpetuate recruitment and activation of myeloid precursors, resulting in unresolved and chronic inflammation. This pathologic inflammation creates profound alterations in the intrinsic cellular metabolism of the myeloid progenitor pool, which is amplified by competition for essential nutrients and by hypoxia-induced metabolic rewiring at the tumor site. Therefore, persistent myelopoiesis and metabolic dysfunctions contribute to the development of cancer, as well as to the severity of a broad range of diseases, including metabolic syndrome and autoimmune and infectious diseases. The aims of this review are to (1) define the metabolic networks implicated in aberrant myelopoiesis observed in cancer patients, (2) discuss the mechanisms underlying these clinical manifestations and the impact of metabolic perturbations on clinical outcomes, and (3) explore new biomarkers and therapeutic strategies to restore immunometabolism and differentiation of myeloid cells towards an effector phenotype to increase host antitumor immunity. We propose that the profound metabolic alterations and associated transcriptional changes triggered by chronic and overactivated immune responses in myeloid cells represent critical factors influencing the balance between therapeutic efficacy and immune-related adverse effects (irAEs) for current therapeutic strategies, including immune checkpoint inhibitor (ICI) therapy.

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“…Furthermore, these studies also showed a preferential inhibition of ω-3 PUFAs for triple negative breast cancer cells rather than luminal breast cancer cells (1,27). Modulation of molecular pathways promoting inflammation is another supposed mechanism by which ω-3 PUFAs can exert anticancer effects (28). Consistent with these observations, some, in vivo studies have reported that specialized pro-resolving lipid mediators (SPMs), which include EPA and DHA-derived resolvins, protectins and maresins, may inhibit chemically-induced colitis in rodents.…”

Section: A C C E P T E D a R T I C L Ementioning

confidence: 87%

Omega-3 PUFAs and gut microbiota: A preventive approach for colorectal cancer

Giammanco

Mazzola²,

Giammanco

et al. 2021

J Biol Res

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The influence of diet on the composition of the intestinal microbiota and related pathologies has been known for some time. Some classes of nutrients, such as fatty acids belonging to the omega 3 series, have particular effects on the bacteria that make up the intestinal microbiota. ω-3 PUFAs affect the gut microbiota in three different ways: by modulating the type and abundance of intestinal bacteria, by regulate SCFAs levels, and by alter the levels of proinflammatory mediators. Through these modalities, ω-3 PUFAs could be useful for the prevention of intestinal diseases such as colorectal cancer (CRC). The ability of ω-3 PUFAs to modulate the intestinal inflammatory response, to preserve the integrity of the intestinal mucosa and to modulate the bacterial composition of the intestine, could be useful as a preventive strategic approach to hinder the development of CRC.

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Fatty Acid Mediators in the Tumor Microenvironment

Cited by 11 publications

References 262 publications

Exogenous Fatty Acids Modulate ER Lipid Composition and Metabolism in Breast Cancer Cells

Exogenous Fatty Acids Modulate ER Lipid Composition and Metabolism in Breast Cancer Cells

Implications of metabolism-driven myeloid dysfunctions in cancer therapy

Omega-3 PUFAs and gut microbiota: A preventive approach for colorectal cancer

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