Low‐Density Lipoproteins, High‐Density Lipoproteins (HDL), and HDL‐Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability

Abstract

Cellular lipid metabolism, lipoprotein interactions, and liver X receptor (LXR) activation have been implicated in the pathophysiology and treatment of cancer, although findings vary across cancer models and by lipoprotein profiles. In this study, we investigated the effects of human-derived low-density lipoproteins (LDL), highdensity lipoproteins (HDL), and HDL-associated proteins apolipoprotein A1 (apoA1) and serum amyloid A (SAA) on markers of viability, cholesterol flux, and differentiation in K562 cells-a bone marrow-derived, stem-like erythroleukemia cell model of chronic myelogenous leukemia (CML). We further evaluated whether lipoprotein-mediated effects were altered by concomitant LXR activation. We observed that LDL promoted higher K562 cell viability in a dose-and time-dependent manner and increased cellular cholesterol concentrations, while LXR activation by the agonist TO901317 ablated these effects. LXR activation in the presence of HDL, apoA1 and SAA-rich HDL suppressed K562 cell viability, while robustly inducing mRNA expression of ATP-binding cassette transporter A1 (ABCA1). HDL and its associated proteins additionally suppressed mRNA expression of anti-apoptotic B-cell lymphoma-extra large (BCL-xL), and the erythroid lineage marker 5 0-aminolevulinate synthase 2 (ALAS2), while SAA-rich HDL induced mRNA expression of the megakaryocytic lineage marker integrin subunit alpha 2b (ITGA2B). Together, these findings suggest that lipoproteins and LXR may impact the viability and characteristics of CML cells.

Lipid Metabolism in Inflammation and Immune Function

“…Further, PI helped to improve detrimental changes in intestinal immune markers but did not fully restore altered microbiome profiles associated with HCC and high-fat feeding. These findings are in line with other studies that highlight the importance of the lipid-immune relationship in cancer pathophysiology [ 8 , 9 ], and provide evidence that diet and non-lipid food components may be used as therapeutic tools in targeting endogenous lipid metabolism to improve immune outcomes within the context of chronic disease.…”

Prognostic significance of pretreatment serum free fatty acid in patients with diffuse large B-cell lymphoma in the rituximab era: a retrospective analysis

“…Metabolism-related genes, processes, and metabolites have essential roles in cancer development and progression [ 8 , 9 ]. Abnormal lipid metabolism has a significant association with the progression of hematological and other malignancies [ 10 , 11 , 18 – 24 ]. Furthermore, statins have demonstrated synergistic antitumor effects in vitro and have improved the survival of patients with several types of cancer, such as DLBCL, bladder cancer, breast cancer, lung cancer, adrenocortical cancer, and T-lymphoma [ 25 – 31 ].…”

“…This result differed from our finding, probably because fatty acid metabolism varies according to age, and the age range of the normal population in our study (14–86 years) differed from that in the study by Zhang et al (18–65 years). Abnormal serum FFA levels were usually found in patients with metabolic diseases, such as diabetes and hyperthyroidism, and more recently, in association with some malignancies [ 10 , 11 , 18 – 24 ]. Studies that have uncovered the relationship between FFAs and cancer also identified the cut-off value of serum FFAs according to cancer diagnosis [ 12 , 13 , 34 ].…”

Consumption of Different Egg-Based Diets Alters Clinical Metabolic and Hematological Parameters in Young, Healthy Men and Women

“…Beyond the potential direct role of egg-derived nutrients on metabolic and hematologic outcome measures, we hypothesized that variable changes in immune and erythrocyte parameters across participants may additionally be a result of improved metabolic profilesspecifically the changes in the concentration of large HDL particles, as HDL has been shown to influence immune cell activation, differentiation, and erythrocyte lifespan [52][53][54][55]. In conducting statistical correlation analysis, we found that changes in specific serum lipid and lipoprotein subclasses differentially correlated with changes in total white blood cell, neutrophil, lymphocyte, and monocyte counts between egg white and whole egg diet periods (Figure 6).…”