Group X secreted phospholipase A2 induces lipid droplet formation and prolongs breast cancer cell survival

Pucer, Anja; Brglez, Vesna; Payré, Christine; Pungerčar, Jože; Lambeau, Gérard; Petan, Toni

doi:10.1186/1476-4598-12-111

Cited by 79 publications

(106 citation statements)

References 82 publications

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“…The presence of lipid-rich serum in the cell culture medium also induces LDs in these cells, but this time in an iPLA 2 β-independent manner because there is an exogenous source free fatty acid [46,52]. This has led to the suggestion that LD formation from endogenous lipid sources upon starvation conditions is a cell mechanism to convert structural components into energy-rich molecules and store them into LD to boost the survival of the cells [21,46,51].…”

Section: Ipla 2 β Role In Ld Formationmentioning

confidence: 96%

“…PLA 2 s may act at several levels, namely (i) as providers of free fatty acids from membrane phospholipids for the synthesis of neutral lipids [46][47][48], (ii) as modifiers of phospholipid-containing particles to facilitate their uptake and internalization by cells [49,50], (iii) as generators of metabolites that may control LD formation [51], and (iv) as direct regulators of the formation of the organelle [52][53][54].…”

Section: Pla 2 and Lipid Dropletsmentioning

confidence: 99%

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Phospholipase A2 regulation of lipid droplet formation

Guijas

Rodríguez

Rubio

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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The classical regard of lipid droplets as mere static energy-storage organelles has evolved dramatically. Nowadays these organelles are known to participate in key processes of cell homeostasis, and their abnormal regulation is linked to several disorders including metabolic diseases (diabetes, obesity, atherosclerosis or hepatic steatosis), inflammatory responses in leukocytes, cancer development and neurodegenerative diseases. Hence, the importance of unraveling the cell mechanisms controlling lipid droplet biosynthesis, homeostasis and degradation seems evident Phospholipase A2s, a family of enzymes whose common feature is to hydrolyze the fatty acid present at the sn-2 position of phospholipids, play pivotal roles in cell signaling and inflammation. These enzymes have recently emerged as key regulators of lipid droplet homeostasis, regulating their formation at different levels. This review summarizes recent results on the roles that various phospholipase A2 forms play in the regulation of lipid droplet biogenesis under different conditions. These roles expand the already wide range of functions that these enzymes play in cell physiology and pathophysiology.

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Section: Ipla 2 β Role In Ld Formationmentioning

confidence: 96%

Section: Pla 2 and Lipid Dropletsmentioning

confidence: 99%

Phospholipase A2 regulation of lipid droplet formation

Guijas

Rodríguez

Rubio

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…For measuring the intracellular amount of lipid droplets in A549 cells treated with SiO 2 -SPIONs (20 and 50 lg/mL) for 48 h, we used Nile red staining and flow cytometry as described previously (Pucer et al, 2013). As a positive control for the induction of intracellular lipid droplet formation, we used 100 lM oleic acid (OA).…”

Section: Measurements Of Cytosolic Lipid Dropletsmentioning

confidence: 99%

“…A reverse transcription was performed using the High Capacity cDNA Reverse Transcripton Kits (Applied Biosystems, Carlsbad, CA) following the manufacturer's protocol. cDNA samples were stored at À20 C. A qPCR relative gene expression analysis was performed as described previously (Pucer et al, 2013) on a StepOnePlus Real-Time by StepOnePlus Real-Time PCR system (Applied Biosystems, Darmstadt, Germany) using the FastStart Universal SYBR Green Master (Rox) from Roche (Mannheim, Germany) and the primers listed in Table S1. DNA topoisomerase 1 (TOP1) and splicing factor 3 A subunit 1 (SF3A1) were used as reference (housekeeping) genes.…”

Section: Transmission Electron Microscopy (Tem)mentioning

confidence: 99%

Harmful at non-cytotoxic concentrations: SiO₂-SPIONs affect surfactant metabolism and lamellar body biogenesis in A549 human alveolar epithelial cells

et al. 2017

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The pulmonary delivery of nanoparticles (NPs) is a promising approach in nanomedicine. For the efficient and safe use of inhalable NPs, understanding of NP interference with lung surfactant metabolism is needed. Lung surfactant is predominantly a phospholipid substance, synthesized in alveolar type II cells (ATII), where it is packed in special organelles, lamellar bodies (LBs). In vitro and in vivo studies have reported NPs impact on surfactant homeostasis, but this phenomenon has not yet been sufficiently examined. We showed that in ATII-like A549 human lung cancer cells, silica-coated superparamagnetic iron oxide NPs (SiO 2 -SPIONs), which have a high potential in medicine, caused an increased cellular amount of acid organelles and phospholipids. In SiO 2 -SPION treated cells, we observed elevated cellular quantity of multivesicular bodies (MVBs), organelles involved in LB biogenesis. In spite of the results indicating increased surfactant production, the cellular quantity of LBs was surprisingly diminished and the majority of the remaining LBs were filled with SiO 2 -SPIONs. Additionally, LBs were detected inside abundant autophagic vacuoles (AVs) and obviously destined for degradation. We also observed time-and dose-dependent changes in mRNA expression for proteins involved in lipid metabolism. Our results demonstrate that non-cytotoxic concentrations of SiO 2 -SPIONs interfere with surfactant metabolism and LB biogenesis, leading to disturbed ability to reduce hypophase surface tension. To ensure the safe use of NPs for pulmonary delivery, we propose that potential NP interference with LB biogenesis is obligatorily taken into account. ARTICLE HISTORY

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“…9 Cells were trypsinized and counted by Trypan blue (Thermo Scientific, USA) exclusion assay 10 using a hemocytometer (Fortuna, Germany). Cells were seeded in 96-well plates (TPP, Switzerland) at a density of 5000 cells/well in 100 μL RPMI-1640 medium and left to attach overnight.…”

Section: Cell Viability Testingmentioning

confidence: 99%

Disintegrins from the Venom of Vipera ammodytes ammodytes Efficiently Inhibit Migration of Breast Cancer Cells

Latinović

Leonardi²,

Petan³

et al. 2017

ACSi

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Integrins are plasma membrane proteins, whose dysfunction frequently results in cancer pathology, and therefore they represent important targets of anti-tumour therapy. Snake venoms are a rich source of disintegrins (Dis), proteins that specifically bind integrins and thus interfere with their functions. In an attempt to discover new molecules for treatment of breast cancer, the major type of cancer in women, we isolated a dimeric Dis (Vaa-Dis) from the venom of the nosehorned viper. By cell viability testing we demonstrated that 50 nM and higher concentrations of Vaa-Dis were toxic to highly invasive human breast adenocarcinoma cell line MDA-MB-231. Wound-healing assay revealed that already at one order of magnitude lower concentrations Vaa-Dis efficiently inhibited MDA-MB-231 cell migration. This exposed a promising anti-metastatic potential of Vaa-Dis and a good perspective of these natural snake venom proteins for further research and development towards the application in breast cancer treatment.

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Group X secreted phospholipase A2 induces lipid droplet formation and prolongs breast cancer cell survival

Cited by 79 publications

References 82 publications

Phospholipase A2 regulation of lipid droplet formation

Phospholipase A2 regulation of lipid droplet formation

Harmful at non-cytotoxic concentrations: SiO₂-SPIONs affect surfactant metabolism and lamellar body biogenesis in A549 human alveolar epithelial cells

Disintegrins from the Venom of Vipera ammodytes ammodytes Efficiently Inhibit Migration of Breast Cancer Cells

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Group X secreted phospholipase A2 induces lipid droplet formation and prolongs breast cancer cell survival

Cited by 79 publications

References 82 publications

Phospholipase A2 regulation of lipid droplet formation

Phospholipase A2 regulation of lipid droplet formation

Harmful at non-cytotoxic concentrations: SiO2-SPIONs affect surfactant metabolism and lamellar body biogenesis in A549 human alveolar epithelial cells

Disintegrins from the Venom of Vipera ammodytes ammodytes Efficiently Inhibit Migration of Breast Cancer Cells

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Harmful at non-cytotoxic concentrations: SiO₂-SPIONs affect surfactant metabolism and lamellar body biogenesis in A549 human alveolar epithelial cells