Sphingolipids in tumor metastases and angiogenesis

Dyatlovitskaya, É. V.; Kandyba, A. G.

doi:10.1134/s0006297906040018

Cited by 20 publications

(13 citation statements)

References 84 publications

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“…This report may allow us to categorize S1P, a bioactive lipid molecule, as a new lymphangiogenic factor. Because several bioactive lipids, including lysophosphatidic acid, sphingosylphosphorylcholine, gangliosides, and sphingomyelin, have proangiogenic activity, 48 investigations of other bioactive lymphangiogenic lipids may be warranted to clarify the mechanisms of lymphangiogenesis. In addition, because chronic inflammation and cancer are highly related to each other, coordinated regulation of lymphangiogenesis and inflammation by S1P suggests that they may be pharmacological targets for development of novel anti-inflammatory and antitumor metastatic therapies.…”

Section: Discussionmentioning

confidence: 99%

Sphingosine-1-phosphate promotes lymphangiogenesis by stimulating S1P1/Gi/PLC/Ca2+ signaling pathways

Yoon

Hong

Moon

et al. 2008

Blood

115

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The lymphatic system plays pivotal roles in mediating tissue fluid homeostasis and immunity, and excessive lymphatic vessel formation is implicated in many pathological conditions, which include inflammation and tumor metastasis. However, the molecular mechanisms that regulate lymphatic vessel formation remain poorly characterized. Sphingosine-1-phosphate (S1P) is a potent bioactive lipid that is implicated in a variety of biologic processes such as inflammatory responses and angiogenesis. Here, we first report that S1P acts as a lymphangiogenic mediator. S1P induced migration, capillarylike tube formation, and intracellular Ca 2؉ mobilization, but not proliferation, in human lymphatic endothelial cells (HLECs) in vitro. Moreover, a Matrigel plug assay demonstrated that S1P promoted the outgrowth of new lymphatic vessels in vivo. HLECs expressed S1P1 and S1P3, and both RNA interference-mediated down-regulation of S1P1 and an S1P1 antagonist significantly blocked S1P-mediated lymphangiogenesis. Furthermore, pertussis toxin, U73122, and BAPTA-AM efficiently blocked S1P-induced in vitro lymphangiogenesis and intracellular Ca 2؉ mobilization of HLECs, indicating that S1P promotes lymphangiogenesis by stimulating S1P1/G i /phospholipase C/Ca 2؉ signaling pathways. Our results suggest that S1P is the first lymphangiogenic bioactive lipid to be identified, and that S1P and its receptors might serve as new therapeutic targets against inflammatory diseases and lymphatic metastasis in tumors. (Blood. 2008; 112:1129-1138) IntroductionSphingosine-1-phosphate (S1P) has been implicated in a wide spectrum of biologic processes, including the promotion of cell growth and survival, migration and differentiation, platelet aggregation, inflammatory responses, and angiogenesis. 1 S1P is generated by the phosphorylation of sphingosine through a process mediated by sphingosine kinase 1 (SphK1) and SphK2. S1P acts both intracellularly as a second messenger 2 and extracellularly as a ligand for a family of G-protein-coupled S1P receptors. 3 S1P1 couples stringently to the G i protein family, whereas S1P2 and S1P3 couple to the G i , G q , and G 12/13 protein families. Multiple interconnections of S1P signaling through S1P1 and S1P3 induce vascular endothelial cell proliferation, migration, morphogenesis, cytoskeletal reorganization, and adherens junction assembly, whereas signaling via S1P2 negatively regulates S1P-mediated multiple responses of vascular endothelial cells. 4 The defective vascular maturation observed in S1P1-deficient mice highlights a fundamental role for S1P signaling on vasculogenesis. 5 Neutralization of the action of extracellular S1P shows significant inhibition of angiogenesis, tumor growth, metastasis, and lymphocyte transmigration, indicating that S1P is an important pathological regulator of inflammation and angiogenesis. [6][7][8] Lymphatic vessels play important roles in mediating tissue fluid homeostasis and immunity. 9 Although lymphangiogenesis, the formation of new lymphatic vessels from preexisting ves...

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Section: Discussionmentioning

confidence: 99%

Sphingosine-1-phosphate promotes lymphangiogenesis by stimulating S1P1/Gi/PLC/Ca2+ signaling pathways

Yoon

Hong

Moon

et al. 2008

Blood

115

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“…Lysosphingo-PL (S1P and SPC) are the key signaling molecules involved in stimulation of cell growth, are potential calcium-mobilizing agonists, induce constriction of capillaries and coronary arteries [1,24].…”

Section: Minor "Signaling" Pl Analyzed By Lipidomic Methodsmentioning

confidence: 99%

Lipidomics: New approaches to the studies of cell signaling and prospects of use in medicine

2007

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A new modern stage in the development of lipid biochemistry is presented: lipidomics, which emerged on the basic of new highly sensitive fractionation methods, primarily, mass spectroscopy. Lipidomics is defined mainly as systemic evaluation of all molecular types of lipids in an object, their cell functions, and molecules with which they react. Lipidomic approaches identifying picomole levels of individual lipids in combination with modern genome technology provide detailed information about the involvement of minor phospholipids in the cell signaling processes. Brief data on the functions of lysophospholipids as second messengers of signal transfer, their effects on cell processes, and possible involvement in the pathogenesis of some diseases are presented. It is expected that introduction of lipidomics in biomedical studies will promote the detection of targets for new drugs and development of new diagnostic tests.

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“…This phenomenon is called Shedding, Gangliosides antigens on the cell surface or in solution (in the cell's surrounding) act as a immunosuppressors and it is proposed that they protect tumor against the host immune system and also increase and enhance metastasis and angiogenesis (Dyatlovitskaya and Kandyba, 2006).…”

Section: Gangliosides and Immune Suppressionmentioning

confidence: 99%

“…Several factors affect this process; gangliosides as both donor molecules and stimulating molecules have different roles in the process of tumor progression and its metastasis. Gangliosides regulate adhesion and movement of the cells strongly, thus initiates tumor metastasis (Dyatlovitskaya and Kandyba, 2006;Nourazarian et al, 2014).…”

Section: Ganglioside Roles In Metastasismentioning

confidence: 99%

Ganglioside as a Therapy Target in Various Types of Cancer

Qamsari¹,

Nourazarian²,

Bagheri³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Since their discovery in 1940, it has been well established that gangliosides are associated with a number of biological pathways and cellular processes such as growth, differentiation and toxin uptake. Gangliosides are glycosphingolipids containing neuraminic acid which are expressed on the plasma membrane of cells particularly in the nervous system. Heterogeneity and structural variation in the carbohydrate chains of gangliosides contributes to unique features of each of these molecules. Thirty five years ago it was discovered that aberrant glycosylation occurs in a variety of human cancers, including aberrant glycosylation of gangliosides. Ganglioside expression in terms of quality and quantity varies in different cancers and different roles may be played. Gangliosides, by affecting the immune system, including esxpression of cytokines and adhesion molecules, may inhibit anti-tumor mechanisms, as well as having direct impact on angiogenesis, cell movement and metastasis. It should be noted that different kinds of gangliosides do not all act by the same mechanisms.

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Sphingolipids in tumor metastases and angiogenesis

Abstract: This review article summarizes data on the involvement of sphingolipids (sphingosine-1-phosphate, sphingosine-1-phosphocholine, neutral glycosphingolipids, and gangliosides) in tumor metastases and angiogenesis.

Cited by 20 publications

References 84 publications

Sphingosine-1-phosphate promotes lymphangiogenesis by stimulating S1P1/Gi/PLC/Ca2+ signaling pathways

Sphingosine-1-phosphate promotes lymphangiogenesis by stimulating S1P1/Gi/PLC/Ca2+ signaling pathways

Lipidomics: New approaches to the studies of cell signaling and prospects of use in medicine

Ganglioside as a Therapy Target in Various Types of Cancer

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