Weight Loss Reversed Obesity-Induced HGF/c-Met Pathway and Basal-Like Breast Cancer Progression

Sundaram, Shanthy; Le, Trinh; Essaid, Luma; Freemerman, Alex J.; Huang, Megan; Galanko, Joseph A.; McNaughton, Kirk K.; Bendt, Katharine M.; Darr, David B.; Troester, Melissa A.; Makowski, Liza

doi:10.3389/fonc.2014.00175

Cited by 34 publications

(44 citation statements)

References 62 publications

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“…And an experiment using the C3(1)-T Ag murine model demonstrated that weight loss could prevent basal-like breast cancer by blocking the obesity-responsive pro-tumorigenic hepatocyte growth factor/c-Met pathway 41 . Thus, theoretically, obesity may increase both luminal and triple-negative tumor risk in premenopausal and postmenopausal women.…”

Section: Discussionmentioning

confidence: 99%

BMI, reproductive factors, and breast cancer molecular subtypes: A case-control study and meta-analysis

Sun

Miller

et al. 2017

Journal of Epidemiology

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BackgroundThe effects of body mass index (BMI) and reproductive factors may vary among breast cancer molecular subtypes, evidence of which is lacking in East Asia.MethodsFrom 2002 to 2010, 1256 breast cancer patients and 1416 healthy women were recruited. Anthropometric and reproductive factors were collected from medical charts. Breast cancer subtype was defined by ER, PR, and HER2 status. Polytomous logistic regression was used to evaluate associations between risk factors and breast cancer subtypes, with subgroup analysis by menopausal status. A meta-analysis of relevant published studies in East Asia was also performed.ResultsIn our case-control study, late menarche was negatively associated with luminal tumor risk (Ptrend = 0.03). Higher BMI was associated with risk of both luminal and triple-negative tumors (Ptrend<0.001). Late age at first live birth was associated with a 1.41- to 2.08-fold increased risk of all subtypes, while late menopause increased risk by 2.62–5.56 times. Heterogeneity of these associations was not detected for different menopausal statuses. The meta-analysis revealed a positive dose-response relationship between BMI and risk of both luminal and ER-PR- subtypes (Ptrend<0.05). Early menarche and nulliparity increased luminal tumor risk by 1.39 and 1.26 times, respectively. Non-breastfeeding also increased the risk of all subtypes.ConclusionsFor East Asian women, overweight, late menopause, and lack of breastfeeding appear to increase risk of both luminal and ER−PR− tumors. Early menarche and nulliparity mainly impacted luminal tumor risk. These associations were not impacted by menopausal status.

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Section: Discussionmentioning

confidence: 99%

BMI, reproductive factors, and breast cancer molecular subtypes: A case-control study and meta-analysis

Sun

Miller

et al. 2017

Journal of Epidemiology

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“…Digital images of stained sections were generated by scanning slides using an Aperio Image Scope Digital Slide Scanner (Vista, CA). Total positive DAB staining was quantified in 5 random microscopic fields using Aperio ImageScope Software (Vista, CA and [6,9]).…”

Section: Methodsmentioning

confidence: 99%

Cafeteria diet-induced obesity causes oxidative damage in white adipose

Johnson

Wilkerson

Sampey

et al. 2016

Biochemical and Biophysical Research Communications

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Obesity continues to be one of the most prominent public health dilemmas in the world. The complex interaction among the varied causes of obesity makes it a particularly challenging problem to address. While typical high-fat purified diets successfully induce weight gain in rodents, we have described a more robust model of diet-induced obesity based on feeding rats a diet consisting of highly palatable, energy-dense human junk foods – the “cafeteria” diet (CAF, 45-53% kcal from fat). We previously reported that CAF-fed rats became hyperphagic, gained more weight, and developed more severe hyperinsulinemia, hyperglycemia, and glucose intolerance compared to the lard-based 45% kcal from fat high fat diet–fed group. In addition, the CAF diet-fed group displayed a higher degree of inflammation in adipose and liver, mitochondrial dysfunction, and an increased concentration of lipid-derived, pro-inflammatory mediators. Building upon our previous findings, we aimed to determine mechanisms that underlie physiologic findings in the CAF diet. We investigated the effect of CAF diet-induced obesity on adipose tissue specifically using expression arrays and immunohistochemistry. Genomic evidence indicated the CAF diet induced alterations in the white adipose gene transcriptome, with notable suppression of glutathione-related genes and pathways involved in mitigating oxidative stress. Immunohistochemical analysis indicated a doubling in adipose lipid peroxidation marker 4-HNE levels compared to rats that remained lean on control standard chow diet. Our data indicates that the CAF diet drives an increase in oxidative damage in white adipose tissue that may affect tissue homeostasis. Oxidative stress drives activation of inflammatory kinases that can perturb insulin signaling leading to glucose intolerance and diabetes.

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“…While the majority of preclinical studies randomize mice to CR from the outset, two preclinical studies have specifically tested the impact of diet-induced obesity followed by weight loss, by incorporating a diet switch during the intervention period. Interestingly, these studies reported contrasting findings, with one reporting that weight loss reversed the tumor-promoting effect of obesity (Sundaram, et al 2014b), and the other reporting the weight loss did not impact obesity-fueled tumor growth (De Angel, et al 2013). Key differences between studies included the degree of obesity attained by the mice and the timing and duration of weight loss, in addition to the use of two different mouse models of basal-like breast cancer, one xenograft (De Angel et al 2013) and the other transgenic (Sundaram et al 2014b).…”

Section: Obesity and Related Co-morbidities As Modifiable Lifestylmentioning

confidence: 99%

“…Interestingly, these studies reported contrasting findings, with one reporting that weight loss reversed the tumor-promoting effect of obesity (Sundaram, et al 2014b), and the other reporting the weight loss did not impact obesity-fueled tumor growth (De Angel, et al 2013). Key differences between studies included the degree of obesity attained by the mice and the timing and duration of weight loss, in addition to the use of two different mouse models of basal-like breast cancer, one xenograft (De Angel et al 2013) and the other transgenic (Sundaram et al 2014b). Discrepant findings such as these may shed light on mechanisms linking weight loss and breast cancer, in addition to informing future study design in both preclinical mouse models and humans.…”

Section: Obesity and Related Co-morbidities As Modifiable Lifestylmentioning

confidence: 99%

Obesity and cancer: mechanistic insights from transdisciplinary studies

Allott¹,

Hursting²

2015

Endocrine-Related Cancer

139

101

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Obesity is associated with a range of health outcomes that are of clinical and public health significance, including cancer. Herein, we summarize epidemiologic and preclinical evidence for an association between obesity and increased risk of breast and prostate cancer incidence and mortality. Moreover, we describe data from observational studies of weight change in humans and from calorie restriction studies in mouse models which support a potential role for weight loss in counteracting tumor-promoting properties of obesity in breast and prostate cancers. Given that weight loss is challenging to achieve and maintain, we also consider evidence linking treatments for obesity-associated co-morbidities, including metformin, statins and non-steroidal anti-inflammatory drugs, with reduced breast and prostate cancer incidence and mortality. Finally, we highlight several challenges that should be considered when conducting epidemiologic and preclinical research in the area of obesity and cancer, including the measurement of obesity in population-based studies, the timing of obesity and weight change in relation to tumor latency and cancer diagnosis, and the heterogeneous nature of obesity and its associated co-morbidities. Given that obesity is a complex trait, comprised of behavioral, epidemiologic and molecular/metabolic factors, we argue that a transdisciplinary approach is the key to understanding the mechanisms linking obesity and cancer. As such, this review highlights the critical need to integrate evidence from both epidemiologic and preclinical studies to gain insight into both biologic and non-biologic mechanisms contributing to the obesity-cancer link.

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Weight Loss Reversed Obesity-Induced HGF/c-Met Pathway and Basal-Like Breast Cancer Progression

Cited by 34 publications

References 62 publications

BMI, reproductive factors, and breast cancer molecular subtypes: A case-control study and meta-analysis

BMI, reproductive factors, and breast cancer molecular subtypes: A case-control study and meta-analysis

Cafeteria diet-induced obesity causes oxidative damage in white adipose

Obesity and cancer: mechanistic insights from transdisciplinary studies

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