A high-fat diet containing lard accelerates prostate cancer progression and reduces survival rate in mice: possible contribution of adipose tissue-derived cytokines.

Han Cho,Heesook Park,Hyerim Song,Gyoo Kwon,Ki Lee,Jung Park,Jung-In Kim

doi:10.3390/nu7042539

Abstract

To examine the effects of high-fat diet (HFD) containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP) and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.

Highlights

According to the World Health Organization, in 2014, approximately 1.9 billion adults were overweight, and at least 600 million adults were obese
Hemoglobin contents in tumor tissues were 23.9 ± 3.0 and 45.6 ± 4.9 in the CD and high-fat diet (HFD) group (p < 0.05), respectively. These results indicate that HFD increases solid tumor growth, angiogenesis, and lymphangiogenesis in the transgenic adenocarcinoma mouse prostate (TRAMP)-C2 allograft model
With well-differentiated carcinoma (WDC) of TRAMP mice in comparison with normal littermates. These increases were further augmented by HFD feeding. These results indicate that HFD feeding stimulates the development of prostate cancer through the induction of cell cycle progression, thereby speeding up the progression to the poorly-differentiated carcinoma (PDC) state in TRAMP mice

Summary

Introduction

According to the World Health Organization, in 2014, approximately 1.9 billion adults were overweight, and at least 600 million adults were obese. Wolin and colleagues estimated that overweight and obesity cause approximately 20% of all cancer cases [1]. Epidemiological studies indicated that obesity is associated with increased risks of several types of cancer, such as colon, breast, and hepatic cancer [2,3]. Studies assessing the link between prostate cancer and obesity have generated puzzling results. A recent review of the epidemiological data linking prostate cancer and obesity indicates that obesity is associated with reduced risk of nonaggressive, indolent disease, and increased risk of more aggressive disease with increased local and distant invasion. Obesity is associated with worse post-treatment results and increased risk of prostate cancer death [5]

Results

Discussion

Conclusion