Sphingosine kinase 1 is up‐regulated in colon carcinogenesis

Kawamori, Toshihiko; Osta, Walid; Johnson, Korey R.; Pettus, Benjamin J.; Bielawski, Jacek; Tanaka, Takuji; Wargovich, Michael J.; Reddy, Bandaru S.; Hannun, Yusuf A.; Obeid, Lina M.; Zhou, Daohong

doi:10.1096/fj.05-4331fje

Cited by 202 publications

(186 citation statements)

References 27 publications

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“…For example, clinical studies have documented expression of ABCC1 in a range of solid and hematological cancers and, in some cases, have correlated its expression with negative responses to treatment and poor disease outcome (36). SphK1 is also up-regulated in many types of cancer (37,38). Moreover, a monoclonal antibody that binds S1P with extremely high affinity and specificity significantly slows tumor progression and associated angiogenesis in several animal models of human cancer (39).…”

Section: Transport Of S1p By Abcc1 Influences Migration Of Mast Cellsmentioning

confidence: 99%

Role of ABCC1 in export of sphingosine-1-phosphate from mast cells

Mitra

Oskeritzian

Payne

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

379

329

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Mast cells play a pivotal role in inflammatory and immediate-type allergic reactions by secreting a variety of potent inflammatory mediators, including sphingosine-1-phosphate (S1P). However, it is not known how S1P is released from cells. Here, we report that S1P is exported from mast cells independently of their degranulation and demonstrate that it is mediated by ATP binding cassette (ABC) transporters. Constitutive and antigen-stimulated S1P release was inhibited by MK571, an inhibitor of ABCC1 (MRP1), but not by inhibitors of ABCB1 (MDR-1, P-glycoprotein). Moreover, downregulation of ABCC1 with small interfering RNA, which decreased its cell surface expression, markedly reduced S1P export from both rat RBL-2H3 and human LAD2 mast cells. Transport of S1P by ABCC1 influenced migration of mast cells toward antigen but not degranulation. These findings have important implications for S1P functions in mast cell-mediated immune responses.secretion ͉ sphingolipids ͉ multidrug resistance ͉ allergic responses ͉ sphingosine kinase S phingosine-1-phosphate (S1P) is a pleiotropic lipid mediator that has been implicated in cancer, immunity, and allergy (1-4). S1P is a ligand for a family of five specific G protein-coupled receptors, designated S1P 1-5 (collectively referred to as S1PRs) (5), through which it regulates many different biological responses, including growth, survival, differentiation, cytoskeleton rearrangements, motility, angiogenesis, vascular maturation, lymphocyte trafficking, and mast cell functions (reviewed in refs. 1-3, 5, and 6). Moreover, like its precursors, sphingosine (Sph) and ceramide, S1P may also have intracellular functions (1, 2, 7). S1P is produced in cells by phosphorylation of Sph, the backbone of all sphingolipids, catalyzed by two closely related Sph kinase (SphK) isoenzymes. SphK1 activity is enhanced by numerous external stimuli, including growth factors, ligands for G protein-coupled receptors, and proinflammatory cytokines, and by cross-linking of Ig receptors (reviewed in refs. 1 and 6). To date, only EGF (8) and cross-linking of Ig receptors (4) have been shown to stimulate SphK2.Although S1P secretion has been demonstrated in only a few types of cells (platelets, astroglial cells, and mast cells) activation of SphK1 involves its translocation to the plasma membrane where its substrate Sph resides (9 -11). Increased S1P formation, in turn, activates S1P receptors on the same and͞or neighboring cells in an autocrine or paracrine manner. It has been demonstrated that this type of ''inside-out'' signaling by S1P is critical for migratory responses of fibroblasts and smooth muscle cells toward PDGF (9, 12) and human breast cancer cells toward EGF (8). Similarly, S1P secreted by mast cells is important for migration of mast cells toward antigen (Ag) and might be involved in the movement of mast cells to sites of inf lammation (13). In addition, S1P provokes human airway smooth muscle contraction and may promote inf lammation and airway remodeling in asthma (14). Because S1P's level...

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Section: Transport Of S1p By Abcc1 Influences Migration Of Mast Cellsmentioning

confidence: 99%

Role of ABCC1 in export of sphingosine-1-phosphate from mast cells

Mitra

Oskeritzian

Payne

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

379

329

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“…These molecules are expressed during tumor neovascularization and promote organization, survival or migration of endothelial cells (23)(24)(25)(26)(27)(28)(29)(30)(31). Other, IL-12-related proangiogenic molecules down-regulated in IL12rb2 ϩ vs. IL12rb2 Ϫ tumors were angiopoietin 1 and 2, eotaxin, procollagen type XVIII␣1, cox1, MMP9, and sphyngosin kinase 1 (32)(33)(34)(35)(36)(37)(38). Finally, IFN-␥ and epiregulin, a major regulator of vascular smooth muscle cell dedifferentiation (39,40), were found to be up-regulated 4.5-and 3.5-fold, respectively, in IL12rb2 ϩ vs. IL12rb2 Ϫ tumors grown in KO mice (Fig.…”

Section: Endogenous Il-12 Dampens Tumorigenicity Of B16 Melanoma Cellsmentioning

confidence: 99%

Endogenous IL-12 triggers an antiangiogenic program in melanoma cells

Airoldi

Carlo

Cocco

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The IL12RB2 gene acts as a tumor suppressor in human B cell malignancies. Indeed, Il12rb2 knockout (KO) mice develop spontaneously B cell tumors, but also lung epithelial tumors. This latter phenotype may be related to (i) impairment of host IL-12-mediated immunosurveillance and/or (ii) IL-12 inability to inhibit directly the growth of IL-12 unresponsive malignant cells. To address this issue, we transplanted IL-12R ؉ B16 melanoma cells into syngeneic Il12rb2 KO mice with the following rationale: (i) these mice have severe defects in IFN-␥ production, as well as in cytotoxic T lymphocyte and natural killer cell cytotoxicity, and (ii) they produce but do not use IL-12 that can potentially bind to and target tumor cells only. Il12rb2 KO mice displayed higher endogenous serum levels of IL-12 and developed smaller B16 tumors than WT animals. These tumors showed reduced proliferation, increased apoptosis, and defective microvessel formation related to down-regulated expression of a set of proangiogenic genes previously unrelated to IL-12. Such effects depended on direct activity of endogenous IL-12 on tumor cells in KO mice, and hydrodynamic delivered IL-12 caused further reduced tumorigenicity of B16 cells in these mice. A previously undescribed mechanism of the IL-12 antitumor activity has been here identified and characterized.angiogenesis ͉ tumor immunology ͉ cytokines I nterleukin 12 is a heterodimeric cytokine bridging innate and adaptive immunity (1). IL-12, which belongs to a family of structurally related cytokines including IL-23 and IL-27 (2, 3), is formed by the IL12p35 and IL12p40 subunits (4) and binds to the IL-12R, composed of the ␤1 and the ␤2 chains. Both chains are needed for high affinity binding of the cytokine and initiation of signal transduction (5, 6). IL12p40 associates with the p19 subunit to form IL-23, which binds to a receptor composed of IL12R␤1 and IL-23R (2, 3). Therefore, the IL12p35 and the IL12R␤2 subunits are unique components of IL-12 and IL-12R, respectively. IL-12, which is produced predominantly by antigen-presenting cells, drives T helper (Th1) responses, enhances T and natural killer (NK) cell cytotoxicity, and induces IFN-␥ production by T and NK cells (4,[7][8][9]. In addition, we have shown that IL-12 contributes to the regulation of normal human B cell function through stimulation of IgM synthesis and IFN-␥ production (10).IL-12 exerts antitumor activity through IFN-␥-dependent and independent mechanisms (11-15), which include modulation of the immune system and antiangiogenesis (16)(17)(18). We have recently demonstrated that the IL12RB2 gene acts as a tumor suppressor in human chronic B cell malignancies (14) and, accordingly, that aging IL12rb2 knockout (KO) mice develop spontaneously B cell tumors. The same mice showed high incidence of lung epithelial tumors. This latter finding may be related to reduced immune surveillance, because of their deficient T and NK cell-mediated cytotoxicity (19), Th2-biased T cell differentiation (20), and/or lack of IL-12-mediated dir...

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“…SphK1 mRNA content was found elevated in cancers, such as lung cancer, glioblastoma and colon carcinoma (Johnson et al, 2005;Van Brocklyn et al, 2005;Kawamori et al, 2006). On the contrary, down-regulation of SphK1 could arrest cell cycle and induce apoptosis (Pchejetski et al, 2005;Bonhoure et al, 2006;Cuvillier et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Reversion of Multidrug Resistance by SKI-II in SGC7901/DDP Cells and Exploration of Underlying Mechanisms

Zhu¹,

Zhu²,

Cai³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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In order to investigate whether SKI-II could reverse drug resistance and its possible mechanisms, we treated SGC7901/DDP cells with SKI-II or SKI-II in combination with DDP. Then cell growth, apoptosis, micromorphological changes, and expression of SphK1, P-gp, NF-κB, Bcl-2 and Bax were assessed by MTT assay, flow cytometry, electron microscopy, immunocytochemistry and Western blot assay respectively. SGC7901/DDP cells were insensitive to cisplatin 2.5mg/L, but when pretreated with SKI-II, their proliferation was inhibited by cisplatin 2.5mg/L significantly, the inhibition rate increasing with time and dose. The apoptosis rate was also significantly elevated. Expression of SphK1 and P-gp was decreased significantly, Pearson correlation analysis showing significant correlation between the two (r=0.595, P<0.01). Expression of NF-κB and Bcl-2 was decreased significantly,while that of Bax was increased, compared to the control group. There were significant correlations between SphK1 and NF-κB(r=0.723, P<0.01), NF-κB and Bcl-2(r=0.768, P<0.01). All these data indicated that SKI-II could reverse drug resistance of SGC7901/DDP to cisplatin by down-regulating expression of P-gp and up-regulating apoptosis through down-regulation of SphK1. The increased apoptotic sensitivity of SGC7901/ DDP to cisplatin was due to the decreasing proportion of Bcl-2/Bax via down-regulating NF-κB.

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Sphingosine kinase 1 is up‐regulated in colon carcinogenesis

Cited by 202 publications

References 27 publications

Role of ABCC1 in export of sphingosine-1-phosphate from mast cells

Role of ABCC1 in export of sphingosine-1-phosphate from mast cells

Endogenous IL-12 triggers an antiangiogenic program in melanoma cells

Reversion of Multidrug Resistance by SKI-II in SGC7901/DDP Cells and Exploration of Underlying Mechanisms

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