Diet-induced macrophage inhibitory cytokine 1 promotes prostate cancer progression

Huang, Mingguo; Narita, Shintaro; Inoue, Takamitsu; Tsuchiya, Norihiko; Satoh, Shigeru; Nanjo, Hiroshi; Sasaki, Takehiko; Habuchi, Tomonori

doi:10.1530/erc-13-0227

Cited by 20 publications

(25 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our current study is the first to illustrate the detrimental effects of a high energy or high fat diet (HED) on ovarian cancer progression. As in other tumor types [46-49], we found that HED promotes an aggressive growth pattern of ovarian tumor spread in the syngeneic ID8 tumor bearing mice. A high tumor burden was observed at most organ sites in HED mice (kidney, liver, spleen, peritoneum and bowel) along with a wider spread to the abdominal adipose tissue and lungs compared to the RD mice (Figs.…”

Section: Discussionsupporting

confidence: 80%

Dietary energy balance modulates ovarian cancer progression and metastasis

et al. 2014

View full text Add to dashboard Cite

A high energy balance, or caloric excess, accounts as a tumor promoting factor, while a negative energy balance via caloric restriction, has been shown to delay cancer progression. The effect of energy balance on ovarian cancer progression was investigated in an isogeneic immunocompetent mouse model of epithelial ovarian cancer kept on a regimen of regular diet, high energy diet (HED) and calorie restricted diet (CRD), prior to inoculating the animals intraperitoneally with the mouse ovarian surface epithelial ID8 cancer cells. Tumor evaluation revealed that mice group on HED displayed the most extensive tumor formation with the highest tumor score at all organ sites (diaphragm, peritoneum, bowel, liver, kidney, spleen), accompanied with increased levels of insulin, leptin, insulin growth factor-1 (IGF-1), monocyte chemoattractant protein-1 (MCP-1), VEGF and interleukin 6 (IL-6). On the other hand, the mice group on CRD exhibited the least tumor burden associated with a significant reduction in levels of insulin, IGF-1, leptin, MCP-1, VEGF and IL-6. Immunohistochemistry analysis of tumors from HED mice showed higher activation of Akt and mTOR with decreased adenosine monophosphate activated kinase (AMPK) and SIRT1 activation, while tumors from the CRD group exhibited the reverse profile. In conclusion, ovarian cancer growth and metastasis occurred more aggressively under HED conditions and was significantly curtailed under CRD. The suggested mechanism involves modulated secretion of growth factors, cytokines and altered regulation of AMPK and SIRT1 that converges on mTOR inhibition. While the role of a high energy state in ovarian cancer has not been confirnmed in the literature, the current findings support investigating the potential impact of diet modulation as adjunct to other anticancer therapies and as possible individualized treatment strategy of epithelial ovarian cancer.

show abstract

Section: Discussionsupporting

confidence: 80%

Dietary energy balance modulates ovarian cancer progression and metastasis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…To determine the relative contribution of the obesity-associated dysregulations of the endocrine metabolic milieu (alterations in the glucose/insulin metabolism and other systemic changes) in the pathologic association between HFD and prostate cancer and in the beneficial antitumoral effects of metformin, we used a mouse model with partial resistance to HFDinduced obesity (16)(17)(18) to be able to analyze the role of the intake of higher fat proportion in the diet (HFD-feeding) and metformin treatment in the progression of xenografted prostate cancer cells without the confounding effects of dysregulated endocrine metabolic conditions. As previously reported, this mouse model did not significantly gain body weight under HFD feeding compared with LFD animals (16-18), which was accompanied by similar body composition and glucose, insulin, and corticosterone levels, with the only observed alteration in leptin levels, which were elevated in HFD-fed mice.…”

Section: Discussionmentioning

confidence: 99%

“…To achieve these goals, we used a combination of different in vivo and in vitro approaches, including the use of a mouse model with partial resistance of HFD-induced obesity (16)(17)(18) to dissect out the role of HFD-feeding or LFD-feeding intake and metformin treatment in the development and progression of xenografted prostate cancer cells without the confounding effects of dysregulated endocrine metabolic conditions as well as, normal-like and/or prostate cancer cell lines to evaluate the in vitro effect of metformin in proliferation, migration, and/or prostate-specific antigen (PSA) secretion.…”

Section: Introductionmentioning

confidence: 99%

Metformin Reduces Prostate Tumor Growth, in a Diet-Dependent Manner, by Modulating Multiple Signaling Pathways

Sarmento‐Cabral

L‐López

Gahete

et al. 2017

Molecular Cancer Research

View full text Add to dashboard Cite

Prostate-cancer is strongly influenced by obesity, wherein metformin could represent a promising treatment; however, the endocrine metabolic/cellular/molecular mechanisms underlying these associations and effects are still unclear. To determine the beneficial antitumoral effects of metformin on prostate cancer progression/aggressiveness and the relative contribution of high-fat diet (HFD; independently of obesity), we used HFD-fed immunosuppressed mice inoculated with PC3 cells (which exhibited partial resistance to diet-induced obesity) compared with low-fat diet (LFD)-fed control mice. Moreover, gene expression analysis was performed on cancer-associated genes in the xenografted tumors, and the antitumorigenic role of metformin on tumoral (PC3/22Rv1/LNCaP) and normal (RWPE1) prostate cells was evaluated. The results demonstrate that HFD is associated with enhanced prostate cancer growth irrespective of body weight gain and endocrine metabolic dysregulations and that metformin can reduce prostate cancer growth under LFD but more prominently under HFD, acting through the modulation of several tumoral-associated processes (e.g., cell cycle, apoptosis, and/or necrosis). Moreover, the actions observed could be mediated by the modulation of the local expression of GH/IGF1 axis components. Finally, it was demonstrated that metformin had disparate effects on proliferation, migration, and prostate-specific antigen secretion from different cell lines. Altogether, these data reveal that metformin inhibits prostate cancer growth under LFD and, specially, under HFD conditions through multiple metabolic/tumoral signaling pathways. The current study linking dietary influence on metformin-regulated signaling pathways and antitumoral response provides new and critical insight on environment-host interactions in cancer and therapy. .

show abstract

“…Furthermore, several studies, including our own, have shown that a HFD and dietary components may alter gene expression, cellular activity, and induce other important changes in circulating biological factors related to PCa aggressiveness [5][6][7].…”

Section: Introductionmentioning

confidence: 95%

“…2b). Considering the accumulating evidence suggesting that palmitic acid (PA) stimulates MIC-1 expression in many types of cancer cells [7,25], we examined the role of increased FFAs on MIC-1 expression under a HFD condition. The mRNA expression level of MIC-1, but not GFRAL and TGF-beta, was signi cantly higher in PCa LNCaP, PC3, and DU145 cells after treatment with 0.125 mmol/l of PA, 0.25 mmol/l of oleic acid (OA), or 0.15 mmol/l of linoleic acid (LA) ( Figure S1 and Fig.…”

Section: Hfd and Exogenous Ffas Enhance The Expression And Secretion mentioning

confidence: 99%

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

Huang

Narita

Koizumi

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Diet-induced macrophage inhibitory cytokine 1 promotes prostate cancer progression

Cited by 20 publications

References 38 publications

Dietary energy balance modulates ovarian cancer progression and metastasis

Dietary energy balance modulates ovarian cancer progression and metastasis

Metformin Reduces Prostate Tumor Growth, in a Diet-Dependent Manner, by Modulating Multiple Signaling Pathways

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

Contact Info

Product

Resources

About