Immune function, mitogenicity, and angiogenic growth factor concentrations in lean and obese rodent sera: implications in obesity-related prostate tumor biology

Mydlo, Jack H.; Gerstein, Matthew; Harris, Charles; Braverman, Alan S.

doi:10.1038/sj.pcan.4500693

Cited by 13 publications

(11 citation statements)

References 19 publications

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“…This motivated us to extend our research to CaP. Several recent studies have shown that chemokines, in particular CXCL12 (SDF-1a), CXCL8 (IL-8), CCL2 (MCP-1), CCL3, (MIP-1a), CCL5 (RANTES), and CXCL10 (IP-10), are produced at the tumor site by the CaP cells that also express their receptors, and commonly also by the supporting tissue (11)(12)(13)(14)(15)(16)(17). These chemokines are likely to promote tumor development and angiogenesis (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”

mentioning

confidence: 99%

Predominant Expression of CCL2 at the Tumor Site of Prostate Cancer Patients Directs a Selective Loss of Immunological Tolerance to CCL2 That Could Be Amplified in a Beneficial Manner

Izhak¹,

Wildbaum²,

Weinberg³

et al. 2009

The Journal of Immunology

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We have previously shown that, during inflammatory autoimmune diseases in humans, the immune system develops a neutralizing auto-Ab–based response to a very limited number of inflammatory mediators, and that amplification of each response could be beneficial for the host. Our working hypothesis has been that this selective breakdown of immunological tolerance is due to a predominant expression of an inflammatory mediator at an immune-restricted site undergoing a destructive process. All three conditions also take place in cancer diseases. In this study, we delineate this hypothesis for the first time in a human cancer disease and then explore its clinical implications. We show that in primary tumor sections of prostate cancer subjects, CCL2 is predominantly expressed at the tumor site over other chemokines that have been associated with tumor development, including: CXCL12, CXCL10, CXCL8, CCL3, and CCL5. Subsequently, the immune response selectivity mounts an Ab-based response to CCL2. These Abs are neutralizing Abs. These findings hold diagnostic and therapeutic implications. The current diagnosis of prostate cancer is based on prostate-specific Ag measurements that do not distinguish benign hypertrophy from malignancy. We show in this study that development of anti-CCL2 Abs is selective to the malignant stage. From a clinically oriented perspective, we show, in an experimental model of the disease, that DNA-based amplification of this response suppresses disease, which has implications for a novel way of therapy in humans.

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mentioning

confidence: 99%

Predominant Expression of CCL2 at the Tumor Site of Prostate Cancer Patients Directs a Selective Loss of Immunological Tolerance to CCL2 That Could Be Amplified in a Beneficial Manner

Izhak¹,

Wildbaum²,

Weinberg³

et al. 2009

The Journal of Immunology

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“…It is not known what physiological mechanisms may underlie an interaction between whole milk and BMI, and it is possible that this statistically significant association was due to chance. Obesity is associated with high circulating levels of VEGF and FGF2, enhancing prostate cancer growth; increased angiogenesis; increased DNA damage; and decreased immune function . Prior research has shown that saturated fat intake, such as that contained in whole milk, increases risk of obesity, particularly in genetically susceptible subgroups .…”

Section: Discussionmentioning

confidence: 99%

Milk and other dairy foods in relation to prostate cancer recurrence: Data from the cancer of the prostate strategic urologic research endeavor (CaPSURE™)

et al. 2017

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Background High‐fat dairy, particularly whole milk, in healthy men may increase risk of aggressive prostate cancer. However, data are limited regarding dairy after prostate cancer diagnosis. Method We conducted a prospective study among 1334 men with non‐metastatic prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor. Men answered a food frequency questionnaire in 2004‐2005 (median 2 years after diagnosis) and were followed until 2016 for recurrence, defined as: prostate cancer death, bone metastases, biochemical recurrence, or secondary treatment. Multivariate Cox proportional hazards regression was used to calculate hazards ratios (HR) and 95% confidence intervals (CI) for associations between whole and low‐fat milk; total, high‐fat, and low‐fat dairy; and other dairy items and risk of recurrence. Results During a median follow‐up of 8 years, we observed 137 events. Men who consumed >4 servings/week versus 0‐3 servings/month of whole milk had an 73% increased risk of recurrence (HR: 1.73; 95%CI: 1.00, 2.98; P‐value = 0.04). Body mass index (BMI) modified the association (P‐interaction = 0.01). Among men with a BMI ≥27 kg/m2, >4 servings/week versus 0‐3 servings/month of whole milk was associated with a 3‐fold higher risk of recurrence (HR: 2.96; 95%CI: 1.58, 5.54; P‐value < 0.001). No association was seen in men with BMI <27 kg/m2. Low‐fat milk and other dairy foods were not associated with recurrence. Conclusion In conclusion, whole milk consumption after prostate cancer diagnosis was associated with increased risk of recurrence, particularly among very overweight or obese men. Men with prostate cancer who choose to drink milk should select non‐fat or low‐fat options.

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“…High levels of adipose tissue correlate with high levels of cholesterol, a precursor for the androgen testosterone, which stimulates epithelial cell proliferation [24, 25]. High adipose levels have also been correlated with high plasma levels of VEGF and FGF2 [26], which both stimulate proliferation of epithelial cells [24, 27, 28]. Adipose tissue also secretes leptin, which has been implicated in enhancing angiogenesis [29] and, consequently, may also enhance tumor development.…”

Section: Discussionmentioning

confidence: 99%

Body mass and smoking are modifiable risk factors for recurrent bladder cancer

Wyszynski

Tanyos

Rees

et al. 2013

Cancer

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Background In the Western world, bladder cancer is the fourth most common cancer in men and the eighth most common in women. Recurrences frequently occur and continued surveillance is necessary to identify and treat recurrent tumors. Efforts to identify risk factors that are potentially modifiable to reduce the rate of recurrence are needed. Methods We investigated cigarette smoking behavior and body mass index (BMI) at diagnosis for associations with bladder cancer recurrence in a population-based study of 726 bladder cancer patients in New Hampshire, US. Patients diagnosed with non-muscle invasive urothelial-cell carcinoma were followed to ascertain long-term prognosis. Analysis of time to recurrence was performed using multivariate Cox regression models. Results Smokers experienced shorter time to recurrence (continuing smoker HR 1.51 95%CI 1.08-2.13). Although being overweight (BMI>24.9 kg/m2) at diagnosis was not a strong independent factor (HR 1.33 95%CI 0.94-1.89), among continuing smokers, being overweight more than doubled the risk of recurrence compared to smokers of normal weight (HR 2.67 95%CI 1.14-6.28). Conclusions These observational results suggest that adiposity is a risk factor for bladder cancer recurrence, particularly among tobacco users. Future intervention studies are warranted to evaluate whether both smoking cessation and weight reduction strategies reduce bladder tumor recurrences.

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Immune function, mitogenicity, and angiogenic growth factor concentrations in lean and obese rodent sera: implications in obesity-related prostate tumor biology

Cited by 13 publications

References 19 publications

Predominant Expression of CCL2 at the Tumor Site of Prostate Cancer Patients Directs a Selective Loss of Immunological Tolerance to CCL2 That Could Be Amplified in a Beneficial Manner

Predominant Expression of CCL2 at the Tumor Site of Prostate Cancer Patients Directs a Selective Loss of Immunological Tolerance to CCL2 That Could Be Amplified in a Beneficial Manner

Milk and other dairy foods in relation to prostate cancer recurrence: Data from the cancer of the prostate strategic urologic research endeavor (CaPSURE™)

Body mass and smoking are modifiable risk factors for recurrent bladder cancer

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