Ceramide and polyunsaturated phospholipids are strongly reduced in human hepatocellular carcinoma

Krautbauer, Sabrina; Meier, Elisabeth M.; Rein-Fischboeck, Lisa; Pohl, Rebekka; Weiss, Thomas S.; Sigrüener, Alexander; Aslanidis, Charalampos; Liebisch, Gerhard; Buechler, Christa

doi:10.1016/j.bbalip.2016.08.014

Cited by 69 publications

(82 citation statements)

References 58 publications

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“…Cer, which is depressed in cancer, acts as a powerful tumor suppressor lipid, so Cer-generated-enzyme activity maybe theoretically weakened in HCC. These data, together with a recent report that showed that HCC tissues are characterized by reduced Cer and increased SM compared with ANLTs and that impaired SMase's activity might be an underlying mechanism of HCC development [12], indicate that low NSMase1 expression might be involved in HCC progression. 1).…”

Section: Discussionsupporting

confidence: 65%

“…Low Cer is associated with tumor progression and poor prognosis in studies of glial tumors and ovarian malignant tumors [10,11]. Krautbauer's group [12] suggested that Cer was significantly decreased in HCC tissues, and SM was greater compared with adjacent nontumorous tissues (ANLT), indicating that Cer and SM are closely associated with HCC. In addition, enzymes involved in ceramide metabolism, including sphingomyelinase, are implicated in the regulation of cancer cell growth and/or survival [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via decreasing the ratio of sphingomyelin/ceramide

et al. 2018

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Neutral sphingomyelinase 1 (NSMase1) mediates caspase-3 activation and apoptosis. However, the role of NSMase1, especially exosome-borne NSMase1 in hepatocellular carcinoma (HCC), remains unclear. We report that NSMase1, which converts sphingomyelin (SM) to ceramide, was significantly downregulated in HCC tissues. Low NSMase1 expression predicted poor long-term survival of HCC patients. NSMase1 downregulation in HCC resulted in increased SM and reduced ceramide (Cer) that led to an increased SM/Cer ratio. Interestingly, NSMase1 and NSMase activity were also decreased in exosomes isolated from HCC tissues and cell lines. Furthermore, NSMase activity increased in exosomes isolated from the culture medium of L02 cells transfected with pEGFP-C3-NSMase1 (NSMase1-Exo). NSMase1-Exo suppressed HCC cell growth and induced apoptosis via reduction of the SM/Cer ratio. Thus, NSMase1 in exosomes inhibits HCC growth by decreasing the SM/Cer ratio.

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via decreasing the ratio of sphingomyelin/ceramide

et al. 2018

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“…The major sphingolipid in mammalian membranes and driver of LR formation is SM, which is comprised of ceramide and phosphorylcholine, and thus SM levels are also affected by aberrant choline metabolism [212]. In fact, SM is increased in multiple cancer tissues, including prostate [213], thyroid [214, 215], cervical [216], brain [217, 218], liver [219-221], breast [222, 223], as well as in lymph node metastases [224], feces from colorectal cancer [225], and urine from bladder cancer [226] patients. Depressed or unchanged SM levels were also detected in other studies [227-230].…”

Section: Rendering the Mdr Phenotype And Altered Sphingolipids: Chmentioning

confidence: 99%

Sphingolipid abnormalities in cancer multidrug resistance: Chicken or egg?

Lee

Kolesnick

2017

Cellular Signalling

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The cancer multidrug resistance (MDR) phenotype encompasses a myriad of molecular, genetic and cellular alterations resulting from progressive oncogenic transformation and selection. Drug efflux transporters, in particular the MDR P-glycoprotein ABCB1, play an important role in MDR but cannot confer the complete phenotype alone indicating parallel alterations are prerequisite. Sphingolipids are essential constituents of lipid raft domains and directly participate in functionalization of transmembrane proteins, including providing an optimal lipid microenvironment for multidrug transporters, and are also perturbed in cancer. Here we postulate that increased sphingomyelin content, developing early in some cancers, recruits and functionalizes plasma membrane ABCB1 conferring a state of partial MDR, which is completed by glycosphingolipid disturbance and the appearance of intracellular vesicular ABCB1. In this review, the independent and interdependent roles of sphingolipid alterations and ABCB1 upregulation during the transformation process and resultant conferment of partial and complete MDR phenotypes are discussed.

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“…Sphingosine 1‐phosphate levels have been reported to be elevated in individuals and mice with SCD (Zhang et al, ). Although CER are altered in acute phase reactions (Memon et al, ), obesity (Turpin et al, ), cancer (Krautbauer et al, ) and renal disorders (Mitsnefes et al, ), limited data are available on serum levels of different CerPCho and CER species in SCD. We had previously shown that the lipid profile was disturbed in SCD patients (Ozturk et al, ).…”

Section: Introductionmentioning

confidence: 99%

Decreased Serum Levels of Sphingomyelins and Ceramides in Sickle Cell Disease Patients

Aslan

Kıraç

Kaya

et al. 2018

Lipids

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Limited data are available on the serum levels of different sphingomyelin (CerPCho) and ceramide (CER) species in sickle-cell disease (SCD). This study was aimed at identifying the levels of C16-C24 CerPCho and C16-C24 CER in serum obtained from SCD patients and controls. Circulating levels of neutral sphingomyelinase (N-SMase) activity, ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P) were also determined. Blood was collected from 35 hemoglobin (Hb)A volunteers and 45 homozygous HbSS patients. Serum levels of C16-C24 CerPCho and C16-C24 CER were determined by an optimized multiple reaction monitoring (MRM) method using ultrafast liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Serum activity of N-SMase was assayed by standard kit methods, and C1P and S1P levels were determined by enzyme-linked immunosorbent assay. A significant decrease was observed in the serum levels of C18-C24 CerPCho in patients with SCD compared to controls. No significant difference was found in C16 CerPCho levels between the two groups. Very-long-chain C22-C24 CER were significantly decreased in SCD, while long-chain C16-C20 CER levels showed no significant difference between SCD patients and controls. Significant positive correlation was found between the serum total cholesterol levels and C18-C24 CerPCho and C22-C24 CER in SCD patients. Patients with SCD had significantly elevated serum activity of N-SMase as well as increased circulating levels of C1P and S1P compared to controls. The decrease in serum levels of C18-C24 CerPCho in patients with SCD was accompanied by decreased levels of C22-C24 CER. Future studies are needed to understand the role of decreased CerPCho and CER in the pathophysiology of SCD.

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Ceramide and polyunsaturated phospholipids are strongly reduced in human hepatocellular carcinoma

Cited by 69 publications

References 58 publications

Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via decreasing the ratio of sphingomyelin/ceramide

Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via decreasing the ratio of sphingomyelin/ceramide

Sphingolipid abnormalities in cancer multidrug resistance: Chicken or egg?

Decreased Serum Levels of Sphingomyelins and Ceramides in Sickle Cell Disease Patients

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