Periprostatic adipose tissue from obese prostate cancer patients promotes tumor and endothelial cell proliferation: A functional and MR imaging pilot study

Venkatasubramanian, Palamadai N.; Brendler, Charles B.; Plunkett, Beth A.; Crawford, Susan E.; Fitchev, Philip; Morgan, Gina; Cornwell, Mona; McGuire, Michael; Wyrwicz, Alice M.; Doll, Jennifer A.

doi:10.1002/pros.22756

Cited by 37 publications

(35 citation statements)

References 48 publications

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“…Other studies have been implemented in cancers of the gastrointestinal tract (colorectal cancer (n=4) (8,64,71,73), esophageal cancer (n=2) (65,79), combined (colorectal and esophageal) (n=1) (80)), reproductive cancer (endometrial (n=1) (72), prostate (n=4) (69,74,81,82)), or ENT tract (tongue (n=1) (83)).…”

Section: Resultsmentioning

confidence: 99%

Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review

Himbert

Delphan

Scherer

et al. 2017

Cancer Prevention Research

153

131

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Obesity and its associated metabolic dysregulation are established risk factors for many cancers. However, the biologic mechanisms underlying this relationship remain incompletely understood. Given the rising rates of both obesity and cancer worldwide, and the challenges for many people to lose excess adipose tissue, a systematic approach to identify potential molecular and metabolic targets is needed to develop effective mechanism-based strategies for the prevention and control of obesity-driven cancer. Epidemiological, clinical, and preclinical data suggest that within the growth-promoting, pro-inflammatory microenvironment accompanying obesity, crosstalk between adipose tissue (comprised of adipocytes, macrophages and other cells) and cancer-prone cells may occur via obesity-associated hormones, cytokines, and other mediators that have been linked to increased cancer risk and/or progression. We report here a systematic review on the direct “crosstalk” between adipose tissue and carcinomas in humans. We identified 4,641 articles with n=20 human clinical studies which are summarized as: (a) breast (n=7), (b) colorectal (n=4), (c) esophageal (n=2), (d) esophageal/colorectal (n=1), (e) endometrial (n=1), (f) prostate (n=4), and (g) ear-nose-throat (ENT) cancer (n=1). Findings from these clinical studies reinforce preclinical data and suggest organ-dependent crosstalk between adipose tissue and carcinomas via VEGF, IL-6, TNF-alpha and other mechanisms. Moreover, visceral white adipose tissue (VAT) plays a more central role as it is more bio-energetically active and is associated with a more pro-cancer secretome than subcutaneous adipose tissue (SAT). Efforts to eavesdrop and ultimately interfere with this cancer-enhancing crosstalk may lead to new targets and strategies for decreasing the burden of obesity-related cancers.

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Section: Resultsmentioning

confidence: 99%

Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review

Himbert

Delphan

Scherer

et al. 2017

Cancer Prevention Research

153

131

View full text Add to dashboard Cite

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“…This view is based on the clinical observation that PPAT quantity is increased in obesity and is a risk factor for both the diagnosis of prostate cancer and predicting high-grade disease [41, 42]. In addition, in vitro studies have reported that factors secreted from PPAT increase proliferation and motility in PC3 prostate cancer cells, and that the PPAT-secreted factors from obese patients are more pro-tumorigenic than those from lean patients [18, 43]. We confirmed and extended on the key results of these in vitro studies by demonstrating pro-tumorigenic effects of PPAT-secreted factors in a cellularized co-culture model that incorporates human primary stromal-epithelial interactions, which more closely mimics the tumor microenvironment [24].…”

Section: Discussionmentioning

confidence: 99%

Obesity does not promote tumorigenesis of localized patient-derived prostate cancer xenografts

Clark

Ascui

et al. 2016

Oncotarget

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There are established epidemiological links between obesity and the severity of prostate cancer. We directly tested this relationship by assessing tumorigenicity of patient-derived xenografts (PDXs) of moderate-grade localized prostate cancer in lean and obese severe combined immunodeficiency (SCID) mice. Mice were rendered obese and insulin resistant by high-fat feeding for 6 weeks prior to transplantation, and PDXs were assessed 10 weeks thereafter. Histological analysis of PDX grafts showed no differences in tumor pathology, prostate-specific antigen, androgen receptor and homeobox protein Nkx-3.1 expression, or proliferation index in lean versus obese mice. Whilst systemic obesity per se did not promote prostate tumorigenicity, we next asked whether the peri-prostatic adipose tissue (PPAT), which covers the prostate anteriorly, plays a role in prostate tumorigenesis. In vitro studies in a cellularized co-culture model of stromal and epithelial cells demonstrated that factors secreted from human PPAT are pro-tumorigenic. Accordingly, we recapitulated the prostate-PPAT spatial relationship by co-grafting human PPAT with prostate cancer in PDX grafts. PDX tissues were harvested 10 weeks after grafting, and histological analysis revealed no evidence of enhanced tumorigenesis with PPAT compared to prostate cancer grafts alone. Altogether, these data demonstrate that prostate cancer tumorigenicity is not accelerated in the setting of diet-induced obesity or in the presence of human PPAT, prompting the need for further work to define the at-risk populations of obesity-driven tumorigenesis and the biological factors linking obesity, adipose tissue and prostate cancer pathogenesis.

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“…Recent studies of hormone receptor positive breast cancer in obese, post-menopausal women have linked obesity, inflammation and increased aromatase activity in breast cancer patients 14 . In another study, peri-prostatic adipose tissue in prostate cancer has recently been shown to influence tumor growth by promoting angiogenesis 16 . In addition, there is evidence that different adipose tissue depots have distinct gene expression profiles and metabolic phenotypes 13 .…”

Section: Introductionmentioning

confidence: 99%

Robust Early Inflammation of the Peripancreatic Visceral Adipose Tissue During Diet-Induced Obesity in the KrasG12D Model of Pancreatic Cancer

Hertzer¹,

Xu²,

Moro³

et al. 2016

Pancreas

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Objectives Obesity increases the incidence of multiple types of cancer. Our previous work has shown that a high fat, high calorie diet (HFCD) leads to visceral obesity, pancreatic inflammation, and accelerated pancreatic neoplasia in KrasG12D (KC) mice. In this study we aimed to investigate the effects of a HFCD on visceral adipose inflammation with emphasis on potential differences between distinct visceral adipose depots. Methods We examined the weight and visceral obesity in both wild-type (WT) and KC mice on either control diet (CD) or HFCD. After three months, mice were sacrificed for histological examination. Multiplex assays were also performed to obtain cytokine profiles between different adipose depots. Results Both WT and KC mice on a HFCD exhibited significantly increased inflammation in the visceral adipose tissue (VAT), particularly in the peri-pancreatic fat (PPF), compared to animals on a CD. This was associated with significantly increased inflammation in the pancreas. Cytokine profiles were different between visceral adipose depots, and between mice on the HFCD and CD. Conclusions Our results clearly demonstrate that a HFCD leads to obesity and inflammation in the VAT, particularly the PPF. These data suggest that obesity-associated inflammation in PPF may accelerate pancreatic neoplasia in KC mouse.

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Periprostatic adipose tissue from obese prostate cancer patients promotes tumor and endothelial cell proliferation: A functional and MR imaging pilot study

Cited by 37 publications

References 48 publications

Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review

Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review

Obesity does not promote tumorigenesis of localized patient-derived prostate cancer xenografts

Robust Early Inflammation of the Peripancreatic Visceral Adipose Tissue During Diet-Induced Obesity in the KrasG12D Model of Pancreatic Cancer

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