scholarly journals Macrophage Inhibitory Cytokine-1 Induced by a High-Fat Diet Promotes Prostate Cancer Progression by Stimulating Tumor Promoting Cytokine Production from Tumor Stromal Cells

2020 ◽  
Author(s):  
Mingguo Huang ◽  
Shintaro Narita ◽  
Atsushi Koizumi ◽  
Taketoshi Nara ◽  
Kazuyuki Numakura ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
High Fat Diet ◽  
Control Diet ◽  
High Body Mass Index ◽  
High Serum ◽  
High Fat ◽  
Stromal Fibroblasts ◽  
Stromal Microenvironment

Abstract Background: Recent studies have indicated that a high-fat diet (HFD) and/or HFD-induced obesity may influence prostate cancer (PCa) progression, but the role of HFD in PCa microenvironment is unclear. Methods: In this study, we investigated the role of HFD on PCa stromal microenvironment using the PC-3M-luc-C6 PCa model mice fed with HFD or control diet, especially focusing on macrophage inhibitory cytokine-1 (MIC-1) and its effect on the tumor microenvironment. In addition, the synergistic effect of periprostatic adipocytes (PPAC), derived from primary PCa patients, on activation and cytokine secretion of prostate stromal fibroblasts were investigated. The expression pattern and role of MIC-1 signaling on human PCa stroma activation and PCa progression were investigated.Results: The HFD consumption stimulated PCa cell growth and invasion as a result of upregulated MIC-1 signaling and subsequent increased secretion of interleukin (IL)-8 and IL-6 from prostate stromal fibroblasts in the PC-3M-luc-C6 PCa model mice. In addition, PPAC directly stimulated MIC-1 production from PC-3 cells and IL-8 secretion in prostate stromal fibroblasts through upregulation of the adipolysis and free fatty acid (FFA) release. The increased serum MIC-1 was significantly correlated with human PCa stroma activation, high serum IL-8, IL-6 and lipase activity, advanced PCa progression, and high body mass index of the patients. Glial-derived neurotrophic factor receptor alpha-like (GFRAL), a specific receptor of MIC-1, was highly expressed in both the cytoplasm and membrane of the PCa cells and the surrounding stromal fibroblasts, and the expression level was decreased by androgen deprivation therapy and chemotherapy. Conclusion: HFD-mediated activation of the PCa stromal microenvironment through metabolically upregulated MIC-1 signaling by increased available free fatty acids may be a critical mechanism of HFD and/or obesity induced PCa progression.

166. MATERNAL OBESITY IS ASSOCIATED WITH AN INCREASED INCIDENCE OF PROSTATE ABNORMALITIES IN ADULT RAT OFFSPRING

2009 ◽  
Vol 21 (9) ◽  
pp. 84
Author(s):  
K. Chiam ◽  
S. Jindal ◽  
N. Ryan ◽  
S. Moretta ◽  
M. De Blasio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Fat Diet ◽  
Control Diet ◽  
Male Offspring ◽  
Female Rats ◽  
World Health ◽  
High Birth Weight ◽  
Healthy Weight ◽  
High Fat ◽  
Increased Risk

The World Health Organization has stated that 75% of adults worldwide are overweight, and in Australia nearly 25% of men are obese. Obesity is associated with an increased risk of cardiovascular disease, type 2 diabetes and cancer, with 30 to 40% of the latter possibly preventable by maintaining a healthy weight (The International Association for the Study of Obesity). Prostate cancer is the most commonly diagnosed cancer in men and there is increasing evidence that obesity increases the risk of prostate cancer mortality. High birth weight, an indication of excess nutrition during foetal development, has been associated with an increased risk of childhood and adult obesity, and for cancer. Using an animal model, we investigated whether obese mothers are more likely to have obese sons who are at an increased risk of developing prostate abnormalities and thus prostate cancer, in adulthood. Female rats were fed with either a control diet (4g fat/kg) or high fat diet (100g fat/kg) from before mating and throughout pregnancy. Prostate tissues were collected from the male offspring at 90 days (post-puberty) and 180 days (young adult). Histological analysis of the day 90 prostates identified hyperplasia in 100% of the ventral lobes (VL) and 64% of the dorsolateral lobes (DLP) in offspring of the maternal high fat group compared to 0% in each respectively, in those of the maternal control diet group. The VL is the most hormone sensitive prostate lobe of the rat, while the DLP is considered the equivalent of the human peripheral zone, the region from which the majority of human prostate cancers arise. These results suggest for the first time that maternal high fat diet may induce prostate abnormalities in male offspring that may in turn, predispose to an increased risk of prostate cancer in later life.

scholarly journals High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
David P. Labbé ◽  
Giorgia Zadra ◽  
Meng Yang ◽  
Jaime M. Reyes ◽  
Charles Y. Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
High Fat Diet ◽  
Cellular Proliferation ◽  
Saturated Fat ◽  
Prostate Cancer Progression ◽  
Transcriptional Program ◽  
High Fat ◽  
Metabolic Alterations ◽  
Increased Risk

Abstract Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked with increased risk of prostate cancer progression and mortality, but the molecular underpinnings of this association are poorly understood. Here, we demonstrate in a murine prostate cancer model, that high-fat diet (HFD) enhances the MYC transcriptional program through metabolic alterations that favour histone H4K20 hypomethylation at the promoter regions of MYC regulated genes, leading to increased cellular proliferation and tumour burden. Saturated fat intake (SFI) is also associated with an enhanced MYC transcriptional signature in prostate cancer patients. The SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, switching from a high-fat to a low-fat diet, attenuates the MYC transcriptional program in mice. Our findings suggest that in primary prostate cancer, dietary SFI contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet.

scholarly journals Effects of obesity and exercise on colon cancer induction and hematopoiesis in mice

2019 ◽  
Vol 316 (2) ◽  
pp. E210-E220 ◽  
Author(s):  
Russell Emmons ◽  
Guanying Xu ◽  
Diego Hernández-Saavedra ◽  
Adam Kriska ◽  
Yuan-Xiang Pan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Fat Diet ◽  
Control Diet ◽  
High Fat ◽  
Preneoplastic Lesions ◽  
Hematopoietic Stem ◽  
Colon Inflammation ◽  
Increased Risk ◽  
Myeloid Progenitor Cells

Obesity-induced inflammation is associated with increased risk for colorectal cancer (CRC). The role of diet and exercise in modulating increased CRC risk in obesity and the potential role of altered hematopoiesis as a contributor to these effects remain unknown. The purpose of this study was to examine how weight loss induced during CRC induction with or without exercise alters CRC initiation and its relationship to altered hematopoiesis. Mice consumed either a control (CON) or a high-fat diet to induce obesity. All mice were then placed on the control diet during CRC induction with azoxymethane (AOM). Following AOM injection, mice originally on the high-fat diet were randomized into sedentary (HF-SED) or exercise trained (HF-EX) conditions. At euthanasia, body weight and fat mass were similar among all three groups ( P < 0.05). Compared with CON and HF-EX, HF-SED developed increased content of preneoplastic lesions ( P < 0.05), and HF-SED had significantly increased markers of colon inflammation compared with CON. Compared with both CON and HF-EX, HF-SED had decreased content of short-term hematopoietic stem cells and increased content of common myeloid progenitor cells (both P < 0.05). Similarly, HF-SED had increased bone marrow adiposity compared with CON and HF-EX ( P < 0.05), and proteomics analysis revealed an increased marker of bone marrow inflammation in HF-SED compared with CON and HF-EX. Our results suggest that the early removal of a high-fat diet reduces CRC incidence when combined with an exercise training intervention. This reduction in risk was related to lower colon inflammation with anti-inflammatory changes in hematopoiesis induced by exercise.

scholarly journals MP66-13 MIR-130A MODULATES HIGH-FAT DIET-INDUCED PROSTATE CANCER PROGRESSION THROUGH THE ACTIVATION OF MET

2016 ◽  
Vol 195 (4S) ◽  
Author(s):  
Taketoshi Nara ◽  
Shintaro Narita ◽  
Huang Mingguo ◽  
Toshiaki Yoshioka ◽  
Koichiro Takayama ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
High Fat Diet ◽  
Prostate Cancer Progression ◽  
High Fat
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