sphingosine-1-phosphate and Melanoma

Morus alba L. has long been used for beauty in many Asian countries and regions, including anti-aging and hyperpigmentation.. This study aimed at the inhibitory effect of Morus alba L. root on melanogenesis in B16F10 melanoma cells and the mechanism involved.. This study evaluated the anti-melanogenic effect of Morus alba L. root extract (MAR) on B16F10 melanoma cells by assessing cell viability, melanin accumulation, cellular tyrosinase activity, intra/inter-cellular S1P levels, cellular S1P-related metabolic enzyme activity, and western blot analysis. In addition, the potential S1P lyase (S1PL) inhibitory constituents in MAR were identified by LC-MS/MS.. Without affecting the viability of B16F10 melanoma cells, MAR inhibited intracellular tyrosinase activity in a dose-dependent manner, thereby reducing the accumulation of melanin. MAR also downregulated the expression level of MITF via activating the ERK signaling pathway. Furthermore, MAR increased the intra/inter-cellular S1P by inhibiting S1PL. Several compounds with inhibitory S1PL activity have been identified in MAR, such as mulberroside A and oxyresveratrol.. The anti-melanogenic effects of MAR mainly involve promoting MITF degradation mediated via S1P-S1PR3-ERK signaling through increasing cellular S1P levels by inhibiting S1PL activity.

Topics: Animals; Cell Line, Tumor; Chromatography, Liquid; Melanins; Melanoma; Melanoma, Experimental; Microphthalmia-Associated Transcription Factor; Monophenol Monooxygenase; Morus; Signal Transduction; Tandem Mass Spectrometry

Topics: Animals; Biphenyl Compounds; Cell Line, Tumor; Cell Survival; Down-Regulation; Drug Resistance, Neoplasm; Drug Synergism; Enzyme Inhibitors; Female; Humans; Lysophospholipids; Melanoma; Mice; Nitrophenols; Phosphotransferases (Alcohol Group Acceptor); Piperazines; Proto-Oncogene Proteins B-raf; Receptors, Lysosphingolipid; Sphingolipids; Sphingosine; Sphingosine-1-Phosphate Receptors; Sulfonamides; Vemurafenib; Xenograft Model Antitumor Assays

Sphingosine-1-phosphate (S1P) is a bioactive lipid that modulates migratory behavior of cells during embryonic development. In addition, S1P might promote tumor progression by enhancing migratory ability and invasiveness of tumor cells. Migration is a complex process that implies cytoskeletal reorganization and formation of structures that enable cell movement. Besides having similar requirements than migration, invasion also involves proteolytic degradation of extracellular matrix (ECM). Matrix metalloproteases (MMPs) have been identified to break down components of the ECM, allowing cancer cells to spread out of the primary tumor. In this chapter, we will describe different techniques to study migration and invasion induced by S1P. To this end, we include detailed protocols of end-point assays to study migration/invasion, and zymography assay to analyze MMP-2 and MMP-9 activity that were standardized in our laboratory in human melanoma cell lines.

Topics: Cell Line, Tumor; Cell Movement; Gene Expression Regulation, Neoplastic; Humans; In Vitro Techniques; Lysophospholipids; Matrix Metalloproteinases; Melanoma; Neoplasm Invasiveness; Sphingosine

Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that regulates many processes in inflammation and cancer. S1P is a ligand for five G-protein-coupled receptors, S1PR1 to -5, and also has important intracellular actions. Previously, we showed that intracellular S1P is involved in tumor necrosis factor alpha (TNF)-induced NF-κB activation in melanoma cell lines that express filamin A (FLNA). Here, we show that extracellular S1P activates NF-κB only in melanoma cells that lack FLNA. In these cells, S1P, but not TNF, promotes IκB kinase (IKK) and p65 phosphorylation, IκBα degradation, p65 nuclear translocation, and NF-κB reporter activity. NF-κB activation induced by S1P was mediated via S1PR1 and S1PR2. Exogenous S1P enhanced the phosphorylation of protein kinase Cδ (PKCδ), and its downregulation reduced S1P-induced the phosphorylation of IKK and p65. In addition, silencing of Bcl10 also inhibited S1P-induced IKK phosphorylation. Surprisingly, S1P reduced Akt activation in melanoma cells that express FLNA, whereas in the absence of FLNA, high phosphorylation levels of Akt were maintained, enabling S1P-mediated NF-κB signaling. In accord, inhibition of Akt suppressed S1P-mediated IKK and p65 phosphorylation and degradation of IκBα. Hence, these results support a negative role of FLNA in S1P-mediated NF-κB activation in melanoma cells through modulation of Akt.

Topics: Cell Line, Tumor; Filamins; Humans; Lysophospholipids; Melanoma; NF-kappa B; Protein Kinase C-delta; Proto-Oncogene Proteins c-akt; Receptors, Lysosphingolipid; Signal Transduction; Sphingosine; Sphingosine-1-Phosphate Receptors

Acid ceramidase (AC) is a lysosomal cysteine amidase that controls sphingolipid signaling by lowering the levels of ceramides and concomitantly increasing those of sphingosine and its bioactive metabolite, sphingosine 1-phosphate. In the present study, we evaluated the role of AC-regulated sphingolipid signaling in melanoma. We found that AC expression is markedly elevated in normal human melanocytes and proliferative melanoma cell lines, compared with other skin cells (keratinocytes and fibroblasts) and non-melanoma cancer cells. High AC expression was also observed in biopsies from human subjects with Stage II melanoma. Immunofluorescence studies revealed that the subcellular localization of AC differs between melanocytes (where it is found in both cytosol and nucleus) and melanoma cells (where it is primarily localized to cytosol). In addition to having high AC levels, melanoma cells generate lower amounts of ceramides than normal melanocytes do. This down-regulation in ceramide production appears to result from suppression of the de novo biosynthesis pathway. To test whether AC might contribute to melanoma cell proliferation, we blocked AC activity using a new potent (IC50 = 12 nM) and stable inhibitor. AC inhibition increased cellular ceramide levels, decreased sphingosine 1-phosphate levels, and acted synergistically with several, albeit not all, antitumoral agents. The results suggest that AC-controlled sphingolipid metabolism may play an important role in the control of melanoma proliferation.

Topics: Acid Ceramidase; Cell Line, Tumor; Cell Proliferation; Cell Survival; Ceramides; Down-Regulation; Enzyme Inhibitors; Fibroblasts; Gene Expression Regulation, Neoplastic; HCT116 Cells; Hep G2 Cells; Humans; Inhibitory Concentration 50; Keratinocytes; Lipids; Lysophospholipids; MCF-7 Cells; Melanocytes; Melanoma; Microscopy, Confocal; Microscopy, Fluorescence; Oxidoreductases; RNA, Small Interfering; Serine C-Palmitoyltransferase; Signal Transduction; Skin Neoplasms; Sphingolipids; Sphingosine; Uracil

Despite progress in the understanding of the biology and genetics of melanoma, no effective treatment against this cancer is available. The adjacent microenvironment has an important role in melanoma progression. Defining the molecular signals that control the bidirectional dialog between malignant cells and the surrounding stroma is crucial for efficient targeted therapy. Our study aimed at defining the role of sphingosine-1-phosphate (S1P) in melanoma-stroma interactions. Transcriptomic analysis of human melanoma cell lines showed increased expression of sphingosine kinase-1 (SPHK1), the enzyme that produces S1P, as compared with normal melanocytes. Such an increase was also observed by immunohistochemistry in melanoma specimens as compared with nevi, and occurred downstream of ERK activation because of BRAF or NRAS mutations. Importantly, migration of melanoma cells was not affected by changes in SPHK1 activity in tumor cells, but was stimulated by comparable modifications of S1P-metabolizing enzymes in cocultured dermal fibroblasts. Reciprocally, incubation of fibroblasts with the conditioned medium from SPHK1-expressing melanoma cells resulted in their differentiation to myofibroblasts, increased production of matrix metalloproteinases and enhanced SPHK1 expression and activity. In vivo tumorigenesis experiments showed that the lack of S1P in the microenvironment prevented the development of orthotopically injected melanoma cells. Finally, local tumor growth and dissemination were enhanced more efficiently by coinjection of wild-type skin fibroblasts than by fibroblasts from Sphk1(-/-) mice. This report is the first to document that SPHK1/S1P modulates the communication between melanoma cells and dermal fibroblasts. Altogether, our findings highlight SPHK1 as a potential therapeutic target in melanoma progression.

Topics: Aldehyde-Lyases; Animals; Cell Communication; Cell Differentiation; Cell Movement; Cell Transformation, Neoplastic; Extracellular Signal-Regulated MAP Kinases; Female; Fibroblasts; Gene Expression Profiling; GTP Phosphohydrolases; HEK293 Cells; Humans; Lysophospholipids; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Melanoma; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Myofibroblasts; Phosphotransferases (Alcohol Group Acceptor); Proto-Oncogene Proteins B-raf; RNA Interference; RNA, Messenger; RNA, Small Interfering; Skin Neoplasms; Sphingosine

Sphingosine kinase (SK), a key enzyme in sphingosine-1-phosphate (S1P) synthesis, is known to be overexpressed in various types of cancer cells. The effects of anticancer agents on SK1/S1P signaling have not yet been fully assessed in melanoma cells. In the present study, we investigated the effects of the combination of FTY720, an S1P receptor antagonist, and cisplatin, a DNA-damaging agent, on the induction of the death of human melanoma cells, as well as the molecular mechanisms involved. The viability of various human melanoma cell lines was examined following treatment with anticancer drugs. The cisplatin-resistant SK-Mel-28 and cisplatin-sensitive A375 cell lines were selected for this analysis. Protein expression and apoptotic rates were evaluated by western blot analysis following treatment with cisplatin and/or FTY720. Following treatment with a combination of FTY720 and cisplatin, cell viability significantly decreased and the expression of apoptosis-associated cleaved poly(ADP-ribose) polymerase (PARP) was significantly higher in comparison to treatment with cisplatin alone in the SK-Mel-28 cells. In addition, the combination of FTY720 and cisplatin reduced the protein expression of SK1 and the phosphorylation levels of phosphoinositide 3-kinase (PI3K), Akt and mTOR in the SK-Mel-28 cells; the expression of epidermal growth factor receptor (EGFR) was also markedly reduced. These findings suggest that FTY720 and cisplatin synergistically induce cell death through the downregulation of the PI3K/Akt/mTOR pathway and the decrease in EGFR expression in SK-Mel-28 cells. Thus, the combination of FTY720 and cisplatin may have therapeutic potential for chemotherapy-resistant melanoma, and the effects are likely exerted through the downregulation of S1P signaling.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; Cisplatin; Down-Regulation; Drug Resistance, Neoplasm; Drug Synergism; ErbB Receptors; Fingolimod Hydrochloride; Humans; Inhibitory Concentration 50; Lysophospholipids; Melanoma; Phosphatidylinositol 3-Kinases; Phosphotransferases (Alcohol Group Acceptor); Propylene Glycols; Signal Transduction; Sphingosine

Resistance to therapies develops rapidly for melanoma leading to more aggressive disease. Therefore, agents are needed that specifically inhibit proteins or pathways controlling the development of this disease, which can be combined, dependent on genes deregulated in a particular patient's tumors. This study shows that elevated sphingosine-1-phosphate (S-1-P) levels resulting from increased activity of sphingosine kinase-1 (SPHK1) occur in advanced melanomas. Targeting SPHK1 using siRNA decreased anchorage-dependent and -independent growth as well as sensitized melanoma cells to apoptosis-inducing agents. Pharmacological SPHK1 inhibitors SKI-I but not SKI-II decreased S-1-P content, elevated ceramide levels, caused a G2-M block and induced apoptotic cell death in melanomas. Targeting SPHK1 using siRNA or the pharmacological agent called SKI-I decreased the levels of pAKT. Furthermore, SKI-I inhibited the expression of CYCLIN D1 protein and increased the activity of caspase-3/7, which in turn led to the degradation of PARP. In animals, SKI-I but not SKI-II retarded melanoma growth by 25-40%. Thus, targeting SPHK1 using siRNAs or SKI-I has therapeutic potential for melanoma treatment either alone or in combination with other targeted agents.

Topics: Animals; Apoptosis; Cell Adhesion; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclin D1; Down-Regulation; Fibroblasts; G1 Phase Cell Cycle Checkpoints; Humans; Lysophospholipids; Melanocytes; Melanoma; Mice; Molecular Targeted Therapy; Phosphotransferases (Alcohol Group Acceptor); Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Resting Phase, Cell Cycle; RNA, Small Interfering; Skin Neoplasms; Sphingosine; Staurosporine; Thiazoles; Up-Regulation; Xenograft Model Antitumor Assays

Previously we demonstrated that sphingosine 1-phosphate receptor 1 (S1PR(1)) played a prominent, but not exclusive, role in enhancing the excitability of small-diameter sensory neurons, suggesting that other S1PRs can modulate neuronal excitability. To examine the potential role of S1PR(2) in regulating neuronal excitability we used the established selective antagonist of S1PR(2), JTE-013. Here we report that exposure to JTE-013 alone produced a significant increase in excitability in a time- and concentration-dependent manner in 70-80% of recorded neurons. Internal perfusion of sensory neurons with guanosine 5'-O-(2-thiodiphosphate) (GDP-β-S) via the recording pipette inhibited the sensitization produced by JTE-013 as well as prostaglandin E(2). Pretreatment with pertussis toxin or the selective S1PR(1) antagonist W146 blocked the sensitization produced by JTE-013. These results indicate that JTE-013 might act as an agonist at other G protein-coupled receptors. In neurons that were sensitized by JTE-013, single-cell RT-PCR studies demonstrated that these neurons did not express the mRNA for S1PR(2). In behavioral studies, injection of JTE-013 into the rat's hindpaw produced a significant increase in the mechanical sensitivity in the ipsilateral, but not contralateral, paw. Injection of JTE-013 did not affect the withdrawal latency to thermal stimulation. Thus JTE-013 augments neuronal excitability independently of S1PR(2) by unknown mechanisms that may involve activation of other G protein-coupled receptors such as S1PR(1). Clearly, further studies are warranted to establish the causal nature of this increased sensitivity, and future studies of neuronal function using JTE-013 should be interpreted with caution.

Topics: Action Potentials; Analysis of Variance; Anilides; Animals; Capsaicin; Cell Line, Tumor; Cell Movement; Dinoprostone; Dose-Response Relationship, Drug; Drug Interactions; Ganglia, Spinal; Guanosine Diphosphate; Hyperalgesia; Lysophospholipids; Male; Melanoma; Mice; Organophosphonates; Pain Threshold; Patch-Clamp Techniques; Pertussis Toxin; Pyrazoles; Pyridines; Rats; Rats, Sprague-Dawley; Receptors, Lysosphingolipid; Sensory Receptor Cells; Sensory System Agents; Sphingosine; Thionucleotides; Time Factors; Wound Healing

The lysophospholipids sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are small lipid molecules with a variety of physiological roles. Additionally, their involvement in the initiation and progression of malignant tumors has been increasingly recognized in recent years. However, the data on the expression of S1P and LPA receptors on different cancer cells are very few. Real-time polymerase chain reaction was used for the analysis of mRNA expression of five S1P((1-5)) and three LPA((1-3)) receptors on a large panel of 13 colon, breast, melanoma, and lung cancer cell lines. Furthermore, the modulation of S1P and LPA receptor mRNA expression was studied upon xenotransplantation of tumor cells into severe combined immunodeficient (SCID) mice. The S1P and LPA receptors were expressed to a variable degree on all tumor cell lines tested (with exception of colon cancer SW480). Most notably, tumor cell lines in vitro expressed S1P(2) mRNA that was down-regulated upon xenotransplantation, whereas LPA(2) receptor mRNA was strongly expressed both in vitro and in vivo (except by breast cancer cells). The latter was especially distinctive for small cell lung tumor cells. The S1P and LPA receptors are differentially expressed on tumor cell lines in vitro. Their expression is modulated upon xenografting into SCID mice in vivo.

Topics: Animals; Breast Neoplasms; Colonic Neoplasms; Endothelium, Vascular; Female; Humans; Immunoenzyme Techniques; Lung Neoplasms; Lysophospholipids; Melanoma; Mice; Mice, SCID; Neoplasm Transplantation; Receptors, Lysophosphatidic Acid; Receptors, Lysosphingolipid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sphingosine; Transplantation, Heterologous; Tumor Cells, Cultured; Umbilical Cord

Sphingosine-1-phosphate (S1P) is a bioactive phospholipid that transmits signals through G-protein-coupled receptors to control cellular differentiation, survival, and several functions of immune cells. S1P is a chemoattractant for NK cells, which are critical members of the immunological tumor surveillance machinery. In this study we analyzed the influence of S1P on the interaction of NK cells with tumor cells such as the human melanoma cell line Hs294T and the Burkitt's lymphoma cell line Raji. We found that S1P inhibited the cytotoxic activity of NK cells. Analysis of signal transduction pathways revealed that S1P induced common signalling pathways of chemotaxins such as Gi protein-dependent actin reorganization and activation of the phosphatidylinositol 3-kinase (PI3K) dependent signal molecules, protein kinase B (PKB/Akt) and glycogen synthase kinase-3beta (GSK-3beta). In contrast to most chemotaxins, S1P is also able to activate Gs-dependent signalling molecules. This signalling cascade involves increase of cAMP levels and protein kinase A (PKA) activation. Additionally, blocking the regulatory subunits of PKA I abrogated the inhibitory effect of S1P, whereas the catalytic subunits were not involved. Our data indicate that S1P may contributes to the tumor escape from NK cell-dependent immunological surveillance machinery.

Topics: Burkitt Lymphoma; Cell Survival; Cells, Cultured; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; GTP-Binding Protein alpha Subunits, Gi-Go; Humans; Immunoblotting; Interleukin-2; Killer Cells, Natural; Lysophospholipids; Melanoma; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Sphingosine

The histone deacetylase inhibitor, trichostatin A (TSA), and the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (Aza-dC), induced epigenetic regulation of sphingosine-1-phosphate (S1P) receptors in human melanoma cells, switching S1P from motility inhibitor to stimulator. Quantitative PCR revealed increased expression of S1P(1) and S1P(3), associated with S1P-induced chemotaxis, and decreased expression of S1P(2), associated with motility inhibition. Expression of lysophosphatidic acid (LPA) receptors was less affected. The TSA effect was reversible suggesting no mutational change, and Aza-dC treatment resulted in demethylation of a putative S1P(1) promoter. S1P receptors, therefore, appear to be susceptible to epigenetic regulation, accompanied by altered cellular functionality.

Topics: Azacitidine; Cell Line, Tumor; Cell Movement; Decitabine; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation; Humans; Hydroxamic Acids; Lysophospholipids; Melanoma; Nerve Tissue Proteins; Receptors, Lysophospholipid; Receptors, Lysosphingolipid; RNA-Binding Proteins; RNA, Messenger; Sphingosine

The bioactive sphingolipid metabolite sphingosine 1-phosphate (S1P), recently was reported to induce apoptosis of some cancer cells and neurons, although it generally known to exert mitogenic and antiapoptotic effects. In this study, we investigated the effects of S1P on the cell growth, melanogenesis, and apoptosis of cultured B16 mouse melanoma cells. In results, S1P was found to induce apoptosis in B16 melanoma cells in a dose- and time-dependent manner, but exerted minimal effects on melanogenesis. Although receptors of sphingosine 1-phosphate (endothelial differentiation gene 1 [Edg]/S1P(1), Edg5/S1P(2), Edg3/S1P(3)) were expressed in B16 melanoma cells, they were shown not to be associated with S1P-induced apoptosis. In addition, pertussis toxin did not block the apoptotic effects of S1P on B16 melanoma cells. S1P induced caspase-3 activation and the extracellular signal-regulated kinase (ERK) activation. Interestingly, the ERK pathway inhibitor, UO126, reversed the apoptotic effects of S1P on B16 melanoma cells. These results suggest that S1P induced apoptosis of B16 melanoma cells via an Edg receptor-independent, pertussis toxin-insensitive pathway, and appears to be associated with the ERK and caspase-3 activation.

Topics: Animals; Apoptosis; Caspase 3; Cell Line; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Lysophospholipids; Melanoma; Mice; Signal Transduction; Sphingosine

A hydroalcoholic extract of fresh term human placenta was found to be mitogenic as well as melanogenic on B16F10 mouse melanoma in an in vitro culture. The extract, a reservoir of a large number of bioactive molecules, was resolved to get the lipid fraction. Its activity was evaluated on B16F10 mouse melanoma by assessing the change in cellular morphology, growth and melanin induction. The lipid fraction, placental total lipid fraction (PTLF) tested in the study employed doses of 0 01 to 200 microg/ml; optimum growth and melanization accompanied by morphological changes were recorded at 10 and 100 microg/ml respectively. At intermediate doses growth and melanization were found to show a pattern of change over between growth and melanization and finally reached at an inverse relation at the respective optimal dose of response. Compared with defined sphingolipids, C(2) ceramide and sphingosine-1-phosphate, the results were mostly corroborative. The duality of biological response of sphingolipids as reported in numerous studies was comparable for the PTLF suggesting that its active component is a sphingolipid and showing its use for pigment recovery in vitiligo.

Topics: Animals; Cell Division; Cell Size; Cell Survival; Humans; Lipids; Lysophospholipids; Melanins; Melanoma; Mice; Placental Extracts; Sphingolipids; Sphingosine; Tumor Cells, Cultured

Our previous work showed that sphingosine 1-phosphate (Sph-1-P) inhibits the cell motility of mouse melanoma B16/F10, and other types of cells at 10-100 nM concentrations. In the present paper, we have identified and characterized specific cell surface binding sites for Sph-1-P in F10 cells. Sph-1-P immobilized on controlled pore glass beads inhibited the motility of F10 cells, suggesting that Sph-1-P acts on the cells from the outside. Binding assays with [3H]Sph-1-P revealed the presence of specific cell surface binding sites for Sph-1-P in F10 cells. Scatchard analysis demonstrated a single class of binding sites for Sph-1-P. The binding of [3H]Sph-1-P to F10 cells was inhibited by the addition of excess unlabeled Sph-1-P but not other natural sphingolipids. The specific binding was also sensitive to treatment with a protease. Using Sph-1-P-immobilized affinity chromatography, we, for the first time, identified 41-kDa and 79-kDa Sph-1-P binding proteins on the melanoma cell surface, although the 41-kDa protein was less specific to Sph-1-P. We demonstrated that pertussis toxin (PTX) treatment did not abolish the motility inhibition by Sph-1-P, suggesting that no PTX-sensitive G-protein is involved in the signaling. Furthermore, Sph-1-P was found to be specifically released from mouse BALB/3T3 clone A31 cells and F10 cells. Collectively, these results strongly suggest that Sph-1-P regulates melanoma cell motility through an extracellular action by specific binding to cell surface receptor protein(s), which is independent of PTX-sensitive G-protein.

Topics: Animals; Binding Sites; Carrier Proteins; Cell Movement; Extracellular Space; Lysophospholipids; Melanoma; Mice; Microspheres; Pertussis Toxin; Receptors, Cell Surface; Sphingosine; Suramin; Tumor Cells, Cultured; Virulence Factors, Bordetella

Sphingosine-1-phosphate (Sph-1-P), the initial product of sphingosine (Sph) catabolism, has been reported to inhibit motility of mouse melanoma B16/F1 and other types of cells at very low concentrations (10-100 nM). Sph-1-P (100 nM-1 microM) inhibited pseudopodium formation by blocking polymerization and reorganization of actin filaments in newly formed pseudopodia, and reduced F-actin by approximately 25% in F1 cells. A pyrene-labeled actin nucleation assay revealed that Sph-1-P (100 nM) inhibits actin nucleation mediated by F1 cell plasma membranes. These results suggest that Sph-1-P interacts with molecules associated with actin nucleation to inhibit reorganization of pseudopodium formation and cell motility.

Topics: Actins; Animals; Calcium; Cell Membrane; Cell Movement; Culture Media, Conditioned; Lysophospholipids; Melanoma; Mice; Pseudopodia; Sphingosine; Tumor Cells, Cultured