The role of cholesterol metabolism and cholesterol transport in carcinogenesis: a review of scientific findings, relevant to future cancer therapeutics

Pedro M R Cruz,Walter J Mcconathy,Andras G Lacko,Nirupama Sabnis,Huanbiao Mo

doi:10.3389/fphar.2013.00119

Abstract

While the unique metabolic activities of malignant tissues as potential targets for cancer therapeutics has been the subject of several recent reviews, the role of cholesterol metabolism in this context is yet to be fully explored. Cholesterol is an essential component of mammalian cell membranes as well as a precursor of bile acids and steroid hormones. The hypothesis that cancer cells need excess cholesterol and intermediates of the cholesterol biosynthesis pathway to maintain a high level of proliferation is well accepted, however the mechanisms by which malignant cells and tissues reprogram cholesterol synthesis, uptake and efflux are yet to be fully elucidated as potential therapeutic targets. High and low density plasma lipoproteins are the likely major suppliers of cholesterol to cancer cells and tumors, potentially via receptor mediated mechanisms. This review is primarily focused on the role(s) of lipoproteins in carcinogenesis, and their future roles as drug delivery vehicles for targeted cancer chemotherapy.

Highlights

The term “cancer” designates a series of pathological changes characterized by deregulation of cell cycle and metabolism resulting in uncontrolled proliferation of cells (Teicher et al, 2012)
While a wide range of metabolic pathways have been implicated in the process of carcinogenesis and (Hanahan and Weinberg, 2011) as potential targets for cancer prevention, diagnosis or treatment, relatively little has been written about the role(s) of cholesterol biosynthesis or metabolism in this regard
This hiatus of information is somewhat surprising as blood cholesterol levels [especially high density lipoprotein (HDL) levels] have been consistently shown to be lower in cancer patients (Ho et al, 1978; Vitols et al, 1984, 1990) and tumor membranes were found to be rich in cholesterol (Elegbede and Elson, 1986), suggesting that cholesterol utilization by malignant cells and tumors is an important feature of carcinogenesis and perhaps metastasis (Markel and Brook, 1994; Antalis et al, 2011)

Summary

INTRODUCTION

The term “cancer” designates a series of pathological changes characterized by deregulation of cell cycle and metabolism resulting in uncontrolled proliferation of cells (Teicher et al, 2012). While a wide range of metabolic pathways have been implicated in the process of carcinogenesis and (Hanahan and Weinberg, 2011) as potential targets for cancer prevention, diagnosis or treatment, relatively little has been written about the role(s) of cholesterol biosynthesis or metabolism in this regard. This hiatus of information is somewhat surprising as blood cholesterol levels [especially high density lipoprotein (HDL) levels] have been consistently shown to be lower in cancer patients (Ho et al, 1978; Vitols et al, 1984, 1990) and tumor membranes were found to be rich in cholesterol (Elegbede and Elson, 1986), suggesting that cholesterol utilization by malignant cells and tumors is an important feature of carcinogenesis and perhaps metastasis (Markel and Brook, 1994; Antalis et al, 2011). The purpose of this review is to provide an up to date assessment of the findings involving cholesterol metabolism and transport with a focus on opportunities for cancer therapeutics and tumor imaging

CHOLESTEROL AND CANCER

Cholesterol transport and cancer

CONCLUSIONS