Revealing the Role of High-Density Lipoprotein in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is a highly prevalent malignancy with multifactorial etiology, which includes metabolic alterations as contributors to disease development. Studies have shown that lipid status disorders are involved in colorectal carcinogenesis. In line with this, previous studies have also suggested that the serum high-density lipoprotein cholesterol (HDL-C) level decreases in patients with CRC, but more recently, the focus of investigations has shifted toward the exploration of qualitative properties of HDL in this malignancy. Herein, a comprehensive overview of available evidences regarding the putative role of HDL in CRC will be presented. We will analyze existing findings regarding alterations of HDL-C levels but also HDL particle structure and distribution in CRC. In addition, changes in HDL functionality in this malignancy will be discussed. Moreover, we will focus on the genetic regulation of HDL metabolism, as well as the involvement of HDL in disturbances of cholesterol trafficking in CRC. Finally, possible therapeutic implications related to HDL will be presented. Given the available evidence, future studies are needed to resolve all raised issues concerning the suggested protective role of HDL in CRC, its presumed function as a biomarker, and eventual therapeutic approaches based on HDL.

5-Fluorouracil Treatment of CT26 Colon Cancer Is Compromised by Combined Therapy with IMMODIN

“…Changes in HDL levels, HDL particle distribution, and HDL receptors and modulators have been consistently found in CRC patients [ 61 ]. HDL is, so far, the most complex lipoprotein particle, and it is now clear that its role both in health and in disease also includes an antioxidant, anti-inflammatory, immunomodulatory, anti-apoptotic, and anti-thrombotic functions [ 62 ]. Several studies have shown that HDL particles can stimulate the growth of breast cancer cells in vitro, as well as increase the aggressiveness of malignant tumours in mice [ 63 , 64 ].…”

Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents

“…It has been demonstrated that insulin stimulates proliferation of Caco-2 and HT-29 cell lines [30] but also enhances cholesterol uptake and lipid accumulation in Caco-2 cells through elevation of cholesterol transporter scavenger receptor, class B, type I (SR-BI) mRNA, and protein levels [31]. This latter effect of insulin might be of special interest, noting the increasing demand of malignant cells for cholesterol and evidence of disturbed lipid homeostasis in CRC [32,33]. Molecular mechanisms that directly link insulin action and the onset and progression of CRC are suggested by a number of studies.…”

Blood cholesterol-to-lymphocyte ratio as a novel prognostic marker to predict postoperative overall survival in patients with colorectal cancer

“…For instance, the transcription factor RORγ was found to be up-regulated and activate the cholesterol biosynthesis in triple-negative breast cancer cells [ 9 ]. Additionally, the uptake and the accumulation of cholesterol increase in CRC cells which promote their proliferation, and cancer occurrence and development seem to be associated with the consumption of circulating cholesterol by the tumor [ 10 – 12 ]. Therefore, hypercholesteremia potentially maintains sufficient cholesterol uptaken by tumors that accelerate the growth.…”