Objectives: We previously demonstrated the regulation of epithelial ovarian cancer (EOC) cell invasiveness by the bioactive phospholipid sphingosine 1-phosphate (S1P). Low-dose S1P stimulated invasion like lysophosphatidic acid (LPA), while high-dose S1P inhibited invasion. Here we investigate how cell attachment status affects response to S1P and examine the effects of S1P and LPA on cell-cell and cell-extracellular matrix (ECM) adhesion.
Methods: EOC Dov13 cell invasion, ECM attachment and cell adhesion were tested through in vitro assays of Matrigel invasion and attachment to Matrigel, collagen or cell monolayer. Fractionated membrane and cytoplasmic proteins and biotin-labeled surface proteins were analyzed by western analysis. Actin cytoskeleton and FAK were visualized by immunofluorescence.
Results: S1P (20 muM) inhibited invasion of sustained, attached cells but enhanced that of invading cells. Membrane N-cadherin was depleted upon reattachment to ECM. S1P pretreatment (20 muM) accelerated N-cadherin recovery, while 40 muM LPA or 0.5 muM S1P delayed recovery. Cell-cell adhesion and stress fibers were decreased by LPA and by 0.5 muM S1P but increased by 20 muM S1P. While S1P increased cellular attachment to Matrigel and collagen-I, LPA inhibited attachment to Matrigel. Surface N-cadherin, gamma- and beta-catenins, FAK and integrinbeta1 were altered by both reattachment and treatment with S1P or LPA.
Conclusions: S1P inversely affects invasion of attached and invading cells, switching from inhibition to stimulation. This switch is associated with depletion of N-cadherin and membrane FAK. The recovery of membrane N-cadherin, change in cell-cell adhesion and actin stress fibers intensity in response to LPA and S1P inversely correlate with their effects on cellular invasiveness.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ygyno.2007.06.024 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The compensatory enrichment of sphingosine-1-phosphate on HDL in FSGS enhances the protective function of glomerular endothelial cells compared to MCD.
Sci Rep
January 2025
Department of Nephrology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
Glomerular endothelial cells (GECs) are pivotal in developing glomerular sclerosis disorders. The advancement of focal segmental glomerulosclerosis (FSGS) is intimately tied to disruptions in lipid metabolism. Sphingosine-1-phosphate (S1P), a molecule transported by high-density lipoproteins (HDL), exhibits protective effects on vascular endothelial cells by upregulating phosphorylated endothelial nitric oxide synthase (p-eNOS) and enhancing nitric oxide (NO) production.
View Article and Find Full Text PDFCardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis.
BMJ Open Gastroenterol
January 2025
Inflammatory Bowel Disease Center and Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Objective: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). S1P receptor expression on cardiac cells is involved in cardiac conduction. We report cardiovascular treatment-emergent adverse events (TEAEs) associated with S1P receptor modulators and other cardiovascular events in the etrasimod UC clinical programme.
View Article and Find Full Text PDFFloralozone attenuates atherosclerotic vascular injury by regulating AMPKα/SREBP-1c pathway and down-regulating miR-33-5p.
Eur J Nutr
January 2025
College of Pharmacy, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, China.
Background: Severe disruption of lipid metabolism in vivo is one of the central mechanisms in the development of atherosclerotic vascular injury (AVI). Reverse cholesterol transport (RCT) plays a pivotal role in eliminating excess cholesterol, preventing lipid deposition in the aorta, and reducing plaque formation associated with AVI. Floralozone (FL) reduces endothelial cell injury in AVI rats by regulating sphingosine-1-phosphate (S1P) expression.
View Article and Find Full Text PDFSphingosine kinase 2 (SphK2) depletion alters redox metabolism and enhances inflammation in a diet-induced MASH mouse model.
Hepatol Commun
December 2024
Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
Background: Sphingosine-1 phosphate (S1P) is a bioactive lipid molecule that modulates inflammation and hepatic lipid metabolism in MASLD, which affects 1 in 3 people and increases the risk of liver fibrosis and hepatic cancer. S1P can be generated by 2 isoforms of sphingosine kinase (SphK). SphK1 is well-studied in metabolic diseases.
View Article and Find Full Text PDFSparstolonin B Reduces Estrogen-Dependent Proliferation in Cancer Cells: Possible Role of Ceramide and PI3K/AKT/mTOR Inhibition.
Pharmaceuticals (Basel)
November 2024
Department of Medical Biochemistry, Faculty of Medicine, Akdeniz University, Antalya 07070, Turkey.
The aim of this study was to determine the effect of Sparstolonin B (SsnB) on cell proliferation and apoptosis in human breast cancer (MCF-7) and human ovarian epithelial cancer (OVCAR-3) cell lines in the presence and absence of estradiol hemihydrate (ES). Phosphoinositol-3 kinase (PI3K), phosphorylated protein kinase B alpha (p-AKT), phosphorylated mTOR (mechanistic target of rapamycin) signaling proteins, and sphingomyelin/ceramide metabolites were also measured within the scope of the study. The anti-proliferative effects of SsnB therapy were evaluated over a range of times and concentrations.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!