Increased Lipoprotein Lipase Activity in Non-small Cell Lung Cancer Tissue Predicts Shorter Patient Survival

Trošt, Zoran; Sok, Mihael; Marc, Janja; Černe, Darko

doi:10.1016/j.arcmed.2009.05.001

Cited by 22 publications

(23 citation statements)

References 20 publications

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“…LPL would hydrolyze triglycerides to fatty acids that the tumor could use as energy source. Indeed, higher LPL activity is inversely correlated with NSCLC patient survival (Trost et al, 2009). Further studies will be necessary to clarify whether the activity of this enzyme is inhibited by the presence of HTO or whether its activity is low due to lower affinity for HTO. )…”

Section: Discussionmentioning

confidence: 99%

The Novel Anticancer Drug Hydroxytriolein Inhibits Lung Cancer Cell Proliferation via a Protein Kinase Cα– and Extracellular Signal-Regulated Kinase 1/2–Dependent Mechanism

Guardiola-Serrano

Beteta-Göbel

Rodríguez-Lorca

et al. 2015

J Pharmacol Exp Ther

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Membrane lipid therapy is a novel approach to rationally design or discover therapeutic molecules that target membrane lipids. This strategy has been used to design synthetic fatty acid analogs that are currently under study in clinical trials for the treatment of cancer. In this context, and with the aim of controlling tumor cell growth, we have designed and synthesized a hydroxylated analog of triolein, hydroxytriolein (HTO). Both triolein and HTO regulate the biophysical properties of model membranes, and they inhibit the growth of non-small-cell lung cancer (NSCLC) cell lines in vitro. The molecular mechanism underlying the antiproliferative effect of HTO involves regulation of the lipid membrane structure, protein kinase C-a and extracellular signal-regulated kinase activation, the production of reactive oxygen species, and autophagy. In vivo studies on a mouse model of NSCLC showed that HTO, but not triolein, impairs tumor growth, which could be associated with the relative resistance of HTO to enzymatic degradation. The data presented explain in part why olive oil (whose main component is the triacylglycerol triolein) is preventive but not therapeutic, and they demonstrate a potent effect of HTO against cancer. HTO shows a good safety profile, it can be administered orally, and it does not induce nontumor cell (fibroblast) death in vitro or side effects in mice, reflecting its specificity for cancer cells. For these reasons, HTO is a good candidate as a drug to combat cancer that acts by regulating lipid structure and function in the cancer cell membrane.

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Section: Discussionmentioning

confidence: 99%

The Novel Anticancer Drug Hydroxytriolein Inhibits Lung Cancer Cell Proliferation via a Protein Kinase Cα– and Extracellular Signal-Regulated Kinase 1/2–Dependent Mechanism

Guardiola-Serrano

Beteta-Göbel

Rodríguez-Lorca

et al. 2015

J Pharmacol Exp Ther

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“…There is already evidence suggesting FAS and LPL involvement in tumor progression [7,[9][10][11][12][13]. Our previous study demonstrated that FAS activity levels were significantly higher in cancer than in the corresponding normal colorectal mucosa [13], demonstrating that FAS is a functionally active enzyme and that the entire fatty acid synthesis pathway is up-regulated in colorectal carcinoma.…”

Section: Discussionmentioning

confidence: 96%

“…Adipose tissue LPL plays a pivotal role in lipid metabolism and changes in LPL expression could affect both the rate of fat accumulation and the metabolism of triglyceride-rich lipoproteins [3]. In patients with resectable non-small cell lung cancer, higher levels of LPL activity have been detected in cancer tissue than in adjacent non-cancer lung tissue [7]. Moreover, increased LPL activity in non-small cell lung cancer tissue predicts M. Notarnicola shorter patient survival, independent of standard prognostic factors [6].…”

Section: Introductionmentioning

confidence: 99%

Low Levels of Lipogenic Enzymes in Peritumoral Adipose Tissue of Colorectal Cancer Patients

Notarnicola¹,

Miccolis²,

Tutino³

et al. 2011

Lipids

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Lipoprotein lipase (LPL) is the crucial enzyme for intravascular catabolism of triglyceride-rich lipoproteins. Fatty acid synthase (FAS) is a key anabolic enzyme that catalyzes the terminal steps in the novo biosynthesis of 18:2n-6. The involvement of both LPL and FAS in tumor biology has been widely demonstrated in different studies and to verify whether there are regional differences in the expression of these enzymes in visceral adipose tissue from patients with colorectal cancer might be representative of events which sustain tumor growth. The objective of this study was to evaluate LPL and FAS activity and expression of their genes in adipose tissue adjacent to neoplasia and distant from it from patients operated for colorectal cancer. LPL enzymatic activity was evaluated by a fluorescent method and FAS activity by a radiometer assay. Reverse-transcription and real-time PCR were used to detect mRNA levels of two enzymes. Our findings show a significant reduction in both LPL and FAS gene expression and activity levels in adipose tissue adjacent to tumor lesion compared to those detected in paired tissue distant from neoplasia. These results underline the influence of tumor microenvironment on lipid metabolism in adipose tissue, demonstrating a tumor-induced impairment in the formation and lipid storing capacity of adipose tissue in patients with colorectal cancer.

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“…The evidence includes the observation that high LPL activity in non-small cell lung cancer (NSCLC) tissue, relative that in adjacent non-cancer lung tissue, is a predictor of shorter patient survival, independently of standard prognostic factors [4,23]. Further, LPL activity is highest in areas containing actively proliferating cells in a variety of human sarcomas and carcinomas [19].…”

Section: Introductionmentioning

confidence: 97%

Lipoprotein lipase in non-small cell lung cancer tissue is highly expressed in a subpopulation of tumor-associated macrophages

Podgornik

Sok

Kern

et al. 2013

Pathology - Research and Practice

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Increased Lipoprotein Lipase Activity in Non-small Cell Lung Cancer Tissue Predicts Shorter Patient Survival

Cited by 22 publications

References 20 publications

The Novel Anticancer Drug Hydroxytriolein Inhibits Lung Cancer Cell Proliferation via a Protein Kinase Cα– and Extracellular Signal-Regulated Kinase 1/2–Dependent Mechanism

The Novel Anticancer Drug Hydroxytriolein Inhibits Lung Cancer Cell Proliferation via a Protein Kinase Cα– and Extracellular Signal-Regulated Kinase 1/2–Dependent Mechanism

Low Levels of Lipogenic Enzymes in Peritumoral Adipose Tissue of Colorectal Cancer Patients

Lipoprotein lipase in non-small cell lung cancer tissue is highly expressed in a subpopulation of tumor-associated macrophages

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