期刊
EXPERT OPINION ON THERAPEUTIC TARGETS
卷 18, 期 1, 页码 95-107出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/14728222.2014.851671
关键词
cancer metastasis; ceramide-1-phosphate; sphingosine-1-phosphate; stem cell homing; stem cell mobilization
资金
- NIH [2R01 DK074720, 1R01HL112788]
- Stella and Henry Hoenig Endowment
- [Maestro 2011/02/A/NZ4/00035]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL112788] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK074720] Funding Source: NIH RePORTER
Introduction: A common feature of many types of cells is their responsiveness to chemotactic gradients of factors for which they express the corresponding receptors. The most studied chemoattractants so far are peptide-based growth factors and a family of cytokines endowed with strong chemotactic properties, called chemokines. However, additional evidence has accumulated that, in addition to these peptide-based chemoattractants, an important role in cell migration is played by bioactive lipids. Areas covered: Solid evidence has accumulated that two bioactive phosphorylated sphingolipids that are derivatives of sphingolipid metabolism, namely sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), are potent chemoattractants for a variety of cells. In this review, we will discuss the effect of these two phosphorylated sphingolipids on the trafficking of normal and malignant cells, and, in particular, we will focus on their role in trafficking of normal hematopoietic stem/progenitor cells. Unlike other mediators, S1P under steady-state conditions maintain a steep gradient between interstitial fluid and peripheral blood and lymph across the endothelial barrier, which is important in the egress of cells from bone marrow. Both S1P and C1P may be upregulated in damaged tissues, which may result in reversal of this gradient. Expert opinion: S1P and C1P are important regulators of the trafficking of normal and malignant cells, and modification of their biological effects will have important applications in optimizing stem cell mobilization and homing, tissue organ/regeneration, and preventing cancer metastasis.
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