The link between obesity and prostate cancer: the leptin pathway and therapeutic perspectives

Ribeiro, Ricardo; Lopes, Carlos; Medeiros, Rui

doi:10.1038/sj.pcan.4500844

Cited by 48 publications

(38 citation statements)

References 72 publications

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“…6,7,35 The effect of leptin on cancer cell in vitro has also been reported. Leptin stimulates the proliferation of breast, prostate and colorectal cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…2 In addition, obesity increases the risk of cancer developing in the prostate, colorectum, breast, endometrium and elsewhere. [3][4][5][6][7] Similarly, the risk of renal cell cancer is increased in patients with diabetes mellitus, a disease closely associated with obesity. 8 These observations are well correlated with the finding that the carcinogen-induced multiplicity of premalignant colonic lesions is increased in db/db obese and diabetic mice.…”

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confidence: 99%

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Severe pulmonary metastasis in obese and diabetic mice

Mori

Sakurai

Choo

et al. 2006

Intl Journal of Cancer

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Although obesity is known as a risk factor for several human cancers, the association of obesity with cancer recurrence and metastasis remains to be characterized. Here, B16-BL6 melanoma and Lewis lung carcinoma cells were intravenously injected into diabetic (db/db) and obese (ob/ob) mice. The number of experimental lung colonies was markedly promoted in these mice when compared with C57BL/6 mice. In contrast, tumor growth at the implanted site was comparable when cells were inoculated orthotopically. The use of B16-BL6 cells stably transfected with the luciferase gene revealed that the increased metastasis reflected a difference mainly within 6 hr after the intravenous inoculation of tumor cells. Administration of recombinant leptin in ob/ob mice abolished the increase in metastasis early on as well as the decrease in the splenic NK cell number. In addition, depletion of NK cells by an anti-asialo-GM1 antibody abrogated the enhanced metastasis in db/db mice. These results demonstrate that metastasis is markedly promoted in diabetic and obese mice mainly because of decreased NK cell function during the early phase of metastasis. ' 2006 Wiley-Liss, Inc.Key words: obesity; metastasis; NK cell; leptin Obesity has become one of the most critical problems in human health, because it can lead to more serious disorders such as cardiovascular disease, pulmonary disorders and metabolic syndrome. 1 Attention has recently been focused on the influence of obesity on carcinogenesis and the progression of cancer. A cohort study in the United States revealed that an increased body-mass index is significantly associated with higher rates of death because of cancer. 2 In addition, obesity increases the risk of cancer developing in the prostate, colorectum, breast, endometrium and elsewhere. [3][4][5][6][7] Similarly, the risk of renal cell cancer is increased in patients with diabetes mellitus, a disease closely associated with obesity. 8 These observations are well correlated with the finding that the carcinogen-induced multiplicity of premalignant colonic lesions is increased in db/db obese and diabetic mice. 9 Metastasis is the major cause of mortality in cancer patients. Maehle et al. reported that breast cancer patients with obesity had a higher risk of lymph node metastases. 10 Although evidence has accumulated of an association of cancer with obesity, the influence of obesity and diabetes on cancer metastasis remains to be investigated. In addition, the mechanisms by which obesity promotes the development and progression of cancer are still unknown. Material and methods MiceMale C57BL/6, C57BL/KsJ-db/db (db/db) and C57BL/6J-ob/ob (ob/ob) mice, 5-6 weeks old, were maintained in a specific pathogen-free barrier facility under laminar airflow conditions with a 12-hr light/dark cycle, a controlled humidity of 55% 6 5% and a temperature of 22°C 6 1°C. This study was conducted in accordance with the standards outlined in the Guidelines for the Care and Use of Laboratory Animals of the University of Toyama. Cell cultureB16-BL6 ...

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“…6,7,35 The effect of leptin on cancer cell in vitro has also been reported. Leptin stimulates the proliferation of breast, prostate and colorectal cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Severe pulmonary metastasis in obese and diabetic mice

Mori

Sakurai

Choo

et al. 2006

Intl Journal of Cancer

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“…42 IGF-1 is involved in angiogenesis, in the development of bone metastases, and in androgen-independent progression of prostate cancer 43 , and leptin induces cellular migration and growth-factor expression in hormone-resistant prostate cancer cells. 44,45 Thus, increased levels of IGF-1 and leptin in obese men may explain an apparent adverse effect of obesity on prostate cancer progression that leads to death. The observation of a positive association between obesity and risk of fatal prostate cancer suggests that, in this select group of particularly aggressive cancers, the adverse effects of excess body fat outweigh hormonal perturbations that potentially may decrease the risk of prostate cancer in obese men.…”

Section: Discussionmentioning

confidence: 99%

Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality

Wright

Chang

Schatzkin

et al. 2007

Cancer

308

258

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The crystalline structure of the heat‐sealed part of oriented polypropylene (OPP) and cast polypropylene (CPP) films was investigated by differential scanning calorimetry, Fourier transform infrared spectroscopy, and thermal mechanical analysis (TMA). The relationship between the crystalline structure and the mechanical properties was analyzed. It was found that the high total crystallinity of both OPP and CPP gave rise to good mechanical properties and that the orientation of the crystalline structure in the OPP film also was an important factor. The optimum condition for heat sealing was the temperature at which total crystallinity was highest while still retaining the crystalline orientation of OPP. The assessment of crystalline orientation by TMA is an innovation initiated by the authors. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 513–519, 2006

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“…2 Adipose tissue may interact with multiple systems believed to have a role in prostate carcinogenesis, including CYP19 (aromatase) conversion of testosterone into estrogens and changes in immune, inflammatory and insulin responses (reviewed in Ribeiro 3 ). However, while obesity has been associated with prostate cancer mortality [4][5][6][7] and prostate-specific antigen (PSA) recurrence following primary treatment, [8][9][10] the relationship between obesity and prostate cancer risk remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Association between prostate-specific antigen and leptin, adiponectin, HbA1c or C-peptide among African-American and Caucasian men

Fowke

Matthews

Buchowski

et al. 2007

Prostate Cancer Prostatic Dis

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Prior studies report slightly lower prostate-specific antigen (PSA) levels among obese men. To understand this effect, we investigated the association between PSA and blood HbA1c, C-peptide, leptin and adiponectin levels in African-American (AA) (n ¼ 121) and Caucasian (CA) (n ¼ 121) men. Among AA men, PSA levels decreased with increasing C-peptide levels (PSA ¼ 0.99, 0.93, 0.75 and 0.53 ng ml À1 across quartiles of C-peptide, respectively; P trend ¼ 0.005). Among CA men, PSA levels decreased with increasing HbA1c (PSA ¼ 0.84, 0.73, 0.77 and 0.45 ng ml À1 across quartiles of HbA1c, respectively; P trend ¼ 0.005). This may suggest that metabolic disturbances related to metabolic syndrome or diabetes affect the ability to detect early-stage prostate cancer.

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The link between obesity and prostate cancer: the leptin pathway and therapeutic perspectives

Cited by 48 publications

References 72 publications

Severe pulmonary metastasis in obese and diabetic mice

Severe pulmonary metastasis in obese and diabetic mice

Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality

Association between prostate-specific antigen and leptin, adiponectin, HbA1c or C-peptide among African-American and Caucasian men

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