scholarly journals Diet, lipids, and antitumor immunity

Author(s):  
Hannah Prendeville ◽  
Lydia Lynch

AbstractTumour growth and dissemination is largely dependent on nutrient availability. It has recently emerged that the tumour microenvironment is rich in a diverse array of lipids that increase in abundance with tumour progression and play a role in promoting tumour growth and metastasis. Here, we describe the pro-tumorigenic roles of lipid uptake, metabolism and synthesis and detail the therapeutic potential of targeting lipid metabolism in cancer. Additionally, we highlight new insights into the distinct immunosuppressive effects of lipids in the tumour microenvironment. Lipids threaten an anti-tumour environment whereby metabolic adaptation to lipid metabolism is linked to immune dysfunction. Finally, we describe the differential effects of commondietary lipids on cancer growth which may uncover a role for specific dietary regimens in association with traditional cancer therapies. Understanding the relationship between dietary lipids, tumour, and immune cells is important in the context of obesity which may reveal a possibility to harness the diet in the treatment of cancers.

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
HaoRan Tang ◽  
Leo Leung ◽  
Grazia Saturno ◽  
Amaya Viros ◽  
Duncan Smith ◽  
...  

Abstract Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the extracellular matrix. LOX overexpression is associated with poor cancer outcomes. Here, we find that LOX regulates the epidermal growth factor receptor (EGFR) to drive tumour progression. We show that LOX regulates EGFR by suppressing TGFβ1 signalling through the secreted protease HTRA1. This increases the expression of Matrilin2 (MATN2), an EGF-like domain-containing protein that traps EGFR at the cell surface to facilitate its activation by EGF. We describe a pharmacological inhibitor of LOX, CCT365623, which disrupts EGFR cell surface retention and delays the growth of primary and metastatic tumour cells in vivo. Thus, we show that LOX regulates EGFR cell surface retention to drive tumour progression, and we validate the therapeutic potential of inhibiting this pathway with the small molecule inhibitor CCT365623.


2011 ◽  
Vol 32 (1) ◽  
pp. 91-104 ◽  
Author(s):  
Anjani Kumar ◽  
Naveen Kumar Vishvakarma ◽  
Abhishek Tyagi ◽  
Alok Chandra Bharti ◽  
Sukh Mahendra Singh

The present study explores the potential of the anti-neoplastic action of aspirin in a transplantable murine tumour model of a spontaneously originated T-cell lymphoma designated as Dalton's lymphoma. The antitumour action of aspirin administered to tumour-bearing mice through oral and/or intraperitoneal (intratumoral) routes was measured via estimation of survival of tumour-bearing mice, tumour cell viability, tumour progression and changes in the tumour microenvironment. Intratumour administration of aspirin examined to assess its therapeutic potential resulted in retardation of tumour progression in tumour-bearing mice. Oral administration of aspirin to mice as a prophylactic measure prior to tumour transplantation further primed the anti-neoplastic action of aspirin administered at the tumour site. The anti-neoplastic action of aspirin was associated with a decline in tumour cell survival, augmented induction of apoptosis and nuclear shrinkage. Tumour cells of aspirin-treated mice were found arrested in G0/G1 phase of the cell cycle and showed nuclear localization of cyclin B1. Intratumoral administration of aspirin was accompanied by alterations in the biophysical, biochemical and immunological composition of the tumour microenvironment with respect to pH, level of dissolved O2, glucose, lactate, nitric oxide, IFNγ (interferon γ), IL-4 (interleukin-4), IL-6 and IL-10, whereas the TGF-β (tumour growth factor-β) level was unaltered. Tumour cells obtained from aspirin-treated tumour-bearing mice demonstrated an altered expression of pH regulators monocarboxylate transporter-1 and V-ATPase along with alteration in the level of cell survival regulatory molecules such as survivin, vascular endothelial growth factor, heat-shock protein 70, glucose transporter-1, SOCS-5 (suppressor of cytokine signalling-5), HIF-1α (hypoxia-inducible factor-1α) and PUMA (p53 up-regulated modulator of apoptosis). The study demonstrates a possible indirect involvement of the tumour microenvironment in addition to a direct but limited anti-neoplastic action of aspirin in the retardation of tumour growth.


2021 ◽  
Vol 11 ◽  
Author(s):  
Emily J. Kay ◽  
Grigorios Koulouras ◽  
Sara Zanivan

Cancer associated fibroblasts (CAFs) are a major component of the tumour microenvironment in most tumours, and are key mediators of the response to tissue damage caused by tumour growth and invasion, contributing to the observation that tumours behave as ‘wounds that do not heal’. CAFs have been shown to play a supporting role in all stages of tumour progression, and this is dependent on the highly secretory phenotype CAFs develop upon activation, of which extracellular matrix (ECM) production is a key element. A collagen rich, stromal ECM has been shown to influence tumour growth and metastasis, exclude immune cells and impede drug delivery, and is associated with poor prognosis in many cancers. CAFs also extensively remodel their metabolism to support cancer cells, however, it is becoming clear that metabolic rewiring also supports intrinsic functions of activated fibroblasts, such as increased ECM production. In this review, we summarise how fibroblasts metabolically regulate ECM production, focussing on collagen production, at the transcriptional, translational and post-translational level, and discuss how this can provide possible strategies for effectively targeting CAF activation and formation of a tumour-promoting stroma.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
M. A. F. Yahaya ◽  
M. A. M. Lila ◽  
S. Ismail ◽  
M. Zainol ◽  
N. A. R. Nik Mohd Afizan

Tumour-associated macrophage (TAM) serves as the site in which most inflammatory cells coreside. It plays an important role in determining the progression and metastasis of a tumour. The characteristic of TAM is largely dependent on the stimuli present in its tumour microenvironment (TME). Under this environment, however, M2 macrophages are found to be in abundance compared to M1 macrophages which later promote tumour progression. Numerous studies have elucidated the relationship between TAM and the progression of tumour; hence, TAM has now been the subject of interest among researchers for anticancer therapy. This review discusses the role of TAM in colorectal cancer (CRC) and some of the potential candidates that could reeducate TAM to fight against CRC. It is with hope that this review will serve as the foundation in understanding TAM in CRC and helping other researchers to select the most suitable candidate to reeducate TAM that could assist in enhancing the tumouricidal activity of M1 macrophage and eventually repress the development of CRC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Bei Zhao ◽  
Xiaodan Hui ◽  
Hairong Zeng ◽  
Yinan Yin ◽  
Jian Huang ◽  
...  

Lung cancer is one of the most common and lethal neoplasms for which very few efficacious treatments are currently available. M1-like polarised tumour-associated macrophages (TAMs) are key mediators to modulate the tumour microenvironment, which play a key role in inhibiting cancer cell growth. Sophoridine, a naturally occurring alkaloid, exerts multiple pharmacological activities including anti-tumour and anti-inflammatory activities, but it has not been characterised as a regulator of tumour microenvironment towards NSCLC. Herein, the regulatory effects of sophoridine on the polarisation of THP-1 cells into TAMs and the anti-tumour effects of sophoridine-stimulated M1 polarised macrophages towards lung cancer cells were carefully investigated both in vitro and in vivo. The results showed that sophoridine could significantly promote M1 polarisation of RAW264.7 and THP-1-derived macrophages, leading to increased expression of pro-inflammatory cytokines and the M1 surface markers CD86 via activating MAPKs signaling pathway. Further investigations showed that sophoridine-stimulated RAW264.7 and THP-1-derived M1 macrophages effectively induced cell apoptosis as well as inhibited the cell colony formation and cell proliferation in both H460 and Lewis lung cancer cells. In Lewis-bearing mice model, sophoridine (15 or 25 mg/kg) significantly inhibited the tumour growth and up-regulated the expression of CD86/F4/80 in tumour tissues. Collectively, the findings clearly demonstrate that sophoridine promoted M1-like polarisation in vitro and in vivo, suggesting that sophoridine held a great therapeutic potential for treating lung cancer.


2020 ◽  
Vol 15 (7) ◽  
pp. 602-606
Author(s):  
Kun Ji ◽  
Ling Ding ◽  
Xi Chen ◽  
Yun Dai ◽  
Fangfang Sun ◽  
...  

Mesenchymal Stem Cells (MSCs) exhibit enormous therapeutic potential because of their indispensable regenerative, reparative, angiogenic, anti-apoptotic, and immunosuppressive properties. MSCs can best differentiate into mesodermal cell lineages, including osteoblasts, adipocytes, muscle cells, endothelial cells and chondrocytes. Specific differentiation of MSCs could be induced through limited conditions. In addition to the relevant differentiation factors, drastic changes also occur in the microenvironment to conduct it in an optimal manner for particular differentiation. Recent evidence suggests that the mitochondria participate in the regulating of direction and process of MSCs differentiation. Therefore, our current review focuses on how mitochondria participate in both osteogenesis and adipogenesis of MSC differentiation. Besides that, in our current review, we try to provide a further understanding of the relationship between the behavior of mitochondria and the direction of MSC differentiation, which could optimize current cellular culturing protocols for further facilitating tissue engineering by adjusting specific conditions of stem cells.


2016 ◽  
Vol 16 (9) ◽  
pp. 1172-1183 ◽  
Author(s):  
Lamia Benguedouar ◽  
Mesbah Lahouel ◽  
Sophie C. Gangloff ◽  
Anne Durlach ◽  
Florent Grange ◽  
...  

Melanoma is the more dangerous skin cancer, and metastatic melanoma still carries poor prognosis. Despite recent therapeutic advances, prolonged survival remains rare and research is still required. Propolis extracts from many countries have attracted a great deal of attention for their biological properties. We here investigated the ability of an ethanolic extract of Algerian propolis (EEP) to control melanoma tumour growth when given to mice bearing B16F1melanoma tumour either as preventive or as therapeutic treatment. EEP given after tumour occurrence increased mice survival (+30%) and reduced tumour growth (-75%). This was associated with a decrease of the Mitotic Index (-75%) and of Ki-67 (-50%) expression. When given either before or both before and after tumour occurrence, EEP reduced tumour growth but without prolonging mice life. Isolation of B16F1 melanoma cells from resected tumour showed that preventive and curative EEP treatments reduced invasiveness by 55% and 40% respectively compared to control. Galangin, one of the most abundant flavonoids in propolis, significantly reduced the number of melanoma cells in vitro and induced autophagy/apoptosis dose dependently. In conclusion, we showed that EEP reduced melanoma tumour progression/dissemination and could extend mice lifespan when used as therapeutic treatment. Then, EEP may help patients with melanoma when used as a complementary therapy to classical treatment for which autophagy is not contraindicated.


2021 ◽  
Vol 15 (1) ◽  
pp. 21-35
Author(s):  
Yana Geng ◽  
Klaas Nico Faber ◽  
Vincent E. de Meijer ◽  
Hans Blokzijl ◽  
Han Moshage

Abstract Background Non-alcoholic fatty liver disease (NAFLD), characterized as excess lipid accumulation in the liver which is not due to alcohol use, has emerged as one of the major health problems around the world. The dysregulated lipid metabolism creates a lipotoxic environment which promotes the development of NAFLD, especially the progression from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). Purposeand Aim This review focuses on the mechanisms of lipid accumulation in the liver, with an emphasis on the metabolic fate of free fatty acids (FFAs) in NAFLD and presents an update on the relevant cellular processes/mechanisms that are involved in lipotoxicity. The changes in the levels of various lipid species that result from the imbalance between lipolysis/lipid uptake/lipogenesis and lipid oxidation/secretion can cause organellar dysfunction, e.g. ER stress, mitochondrial dysfunction, lysosomal dysfunction, JNK activation, secretion of extracellular vesicles (EVs) and aggravate (or be exacerbated by) hypoxia which ultimately lead to cell death. The aim of this review is to provide an overview of how abnormal lipid metabolism leads to lipotoxicity and the cellular mechanisms of lipotoxicity in the context of NAFLD.


Gut ◽  
2021 ◽  
pp. gutjnl-2020-323363
Author(s):  
Ester Pagano ◽  
Joshua E Elias ◽  
Georg Schneditz ◽  
Svetlana Saveljeva ◽  
Lorraine M Holland ◽  
...  

ObjectivePrimary sclerosing cholangitis (PSC) is in 70% of cases associated with inflammatory bowel disease. The hypermorphic T108M variant of the orphan G protein-coupled receptor GPR35 increases risk for PSC and ulcerative colitis (UC), conditions strongly predisposing for inflammation-associated liver and colon cancer. Lack of GPR35 reduces tumour numbers in mouse models of spontaneous and colitis associated cancer. The tumour microenvironment substantially determines tumour growth, and tumour-associated macrophages are crucial for neovascularisation. We aim to understand the role of the GPR35 pathway in the tumour microenvironment of spontaneous and colitis-associated colon cancers.DesignMice lacking GPR35 on their macrophages underwent models of spontaneous colon cancer or colitis-associated cancer. The role of tumour-associated macrophages was then assessed in biochemical and functional assays.ResultsHere, we show that GPR35 on macrophages is a potent amplifier of tumour growth by stimulating neoangiogenesis and tumour tissue remodelling. Deletion of Gpr35 in macrophages profoundly reduces tumour growth in inflammation-associated and spontaneous tumour models caused by mutant tumour suppressor adenomatous polyposis coli. Neoangiogenesis and matrix metalloproteinase activity is promoted by GPR35 via Na/K-ATPase-dependent ion pumping and Src activation, and is selectively inhibited by a GPR35-specific pepducin. Supernatants from human inducible-pluripotent-stem-cell derived macrophages carrying the UC and PSC risk variant stimulate tube formation by enhancing the release of angiogenic factors.ConclusionsActivation of the GPR35 pathway promotes tumour growth via two separate routes, by directly augmenting proliferation in epithelial cells that express the receptor, and by coordinating macrophages’ ability to create a tumour-permissive environment.


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