Lipid droplets: could they be involved in cancer growth and cancer–microenvironment communications?

Abstract

Common characteristics of tumor cells include the reprogramming of glucose and lipid metabolism, especially the upregulation of glycolysis and lipogenesis accompanied by the accumulation of lipid droplets (LDs) predominantly in aggressive cancer cells and their microenvironment, such as the cancer cells and microenvironment in Zajdela ascites hepatoma (ZAH) [1,2]. This work analyzed the hypothesis that LD-rich malignant cells gain an advantage for their survival, growth, and immune escape through cancer-derived LDs acting within malignant cells and their microenvironment in a synergistic manner. The effect can be amplified at hypoxia/acidosis in the tumor microenvironment, which stimulates mainly the accumulation of dispersed LDs in tumor cells [3,4]. Our research, however, found that intracellular LDs and their orderly packed clusters appeared in dividing ZAH cells, whereas surface LD-containing vesicles in ZAH cells acted as a source of extracellular LDs. Could these LDs be involved in cancer unrestricted proliferation and cancer-induced metabolic communications with a microenvironment participating in local immunosuppressive response? Critical analysis of the literature supports a positive answer to these questions and to the proposed hypothesis. ARE LDs ESSENTIAL FOR CANCER PROLIFERATION?In contrast to normal cells that use exogenous fatty acids (FAs) for their needs, most cancer cells, including malignant hepatocytes, are capable of synthesizing FAs themselves. The requirement of lipid for proliferating tumor cells is high for several reasons [1][2][3]. First, lipids repre-

Humanized CD36 mouse model supports the preclinical evaluation of therapeutic candidates targeting CD36

“…CRC with high metastatic potential expresses higher levels of CD36, which promotes CRC metastasis by upregulating MMP28 and increasing E-calmodulin cleavage [16]. Lipid droplets (LD) are a common feature of cancer cell adaptation to TME acidosis and a key driver of increased cancer cell aggressiveness [17]. It was found that acidosis of TME induces plasma membrane transport of CD36 via TGF-β2, which promotes LD formation and enhances metastasis and invasion of CRC [18].…”

“…TME acidosis and a key driver of increased cancer cell aggressiveness [17]. It was found that acidosis of TME induces plasma membrane transport of CD36 via TGF-β2, which promotes LD formation and enhances metastasis and invasion of CRC [18].…”

Stearoyl-CoA Desaturases1 Accelerates Non-Small Cell Lung Cancer Metastasis by Promoting Aromatase Expression to Improve Estrogen Synthesis

“…Stearoyl-CoA desaturase-1 (SCD1) is the rate-limiting enzyme of lipid synthesis, and is located in the endoplasmic reticulum. SCD1 catalyzes the transformation of saturated fatty acids (SFAs) to monounsaturated fatty acids (MUFAs), which are used to synthesize neutral lipids that are stored in ordered intracellular structures called lipid droplets (LDs) [ 8 , 9 , 10 ]. SCD1 enzyme activity produces active, lipid-modified Wnt proteins, which are responsible for the activation form of frizzled receptor ligands for the activity of the Wnt/β-catenin signaling [ 11 , 12 ].…”

Two Polarity-Sensitive Fluorescent Probes Based on Curcumin Analogs for Visualizing Polarity Changes in Lipid Droplets

“…LDs are involved in numerous physiological functions including signaling [ 11 , 12 ], buffering of lipotoxicity [ 13 , 14 ], relief of cellular stress [ 15 , 16 , 17 ], and modulation of inflammatory responses [ 18 , 19 ]. Dysregulation of LDs is associated with diseases such as obesity [ 20 , 21 ], cardiovascular diseases [ 22 , 23 ], non-alcoholic fatty liver disease (NAFLD) [ 24 , 25 , 26 ], diabetes [ 27 , 28 , 29 ], neurodegeneration [ 30 , 31 ], and multiple cancers [ 32 , 33 ]. Dysregulation of LDs is usually accompanied by changes in the internal environment of the LDs.…”