Ceramide 1-phosphate regulates cell migration and invasion of human pancreatic cancer cells

Rivera, Io-Guané; Ordoñez, Marta; Presa, Natalia; Gangoiti, Patricia; Gómez-Larrauri, Ana; Trueba, Miguel; Fox, Todd E.; Kester, Mark; Gómez-Muñoz, Antonio

doi:10.1016/j.bcp.2015.12.009

Cited by 62 publications

(49 citation statements)

References 37 publications

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“…16 The classical intracellular signaling pathways activated by C1P include PI3K/AKT, MAPK ERK1/2, MAPK P38, and NFκB, which are responsible for the chemotactic effect of this sphingolipid in macrophages and pancreatic cancer cells. 15,26,27 In line with this evidence, we here showed that C1P triggers phosphorylation of PI3K/AKT and MAPK ERK1/2, although P38 or NFκB were not affected. Likewise, both C1P-enhaced proliferation and chemotaxis were fully abrogated by pharmacological inhibitors of AKT and ERK1/2, suggesting these pathways as crucial molecular mechanisms mediating C1P proangiogenic action on ECFC.…”

Section: Discussionsupporting

confidence: 88%

“…As mentioned above, C1P is a well-known chemoattractant factor of monocytes, macrophages, 15,26 pancreatic cancer cells, 27 mesenchymal stem cells, 28 endothelial cells, 29 and several murine precursors, including bone marrow-derived endothelial progenitor cells. 9,10 Our data showed that C1P acted as a potent chemoattractant factor for human ECFC and additionally potentiated the chemotactic effect of SDF-1-the major ECFC physiological chemotactic factor.…”

Section: Discussionmentioning

confidence: 98%

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Ceramide 1-Phosphate Protects Endothelial Colony–Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo

Mena

Zubiry

Dizier

et al. 2019

ATVB

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Ceramide 1-phosphate (C1P) is a bioactive sphingolipid highly augmented in damaged tissues. Because of its abilities to stimulate migration of murine bone marrow-derived progenitor cells, it has been suggested that C1P might be involved in tissue regeneration. In the present study, we aimed to investigate whether C1P regulates survival and angiogenic activity of human progenitor cells with great therapeutic potential in regenerative medicine such as endothelial colonyforming cells (ECFCs). APPROACH AND RESULTS: C1P protected ECFC from TNFα (tumor necrosis factor-α)-induced and monosodium urate crystalinduced death and acted as a potent chemoattractant factor through the activation of ERK1/2 (extracellular signal-regulated kinases 1 and 2) and AKT pathways. C1P treatment enhanced ECFC adhesion to collagen type I, an effect that was prevented by β1 integrin blockade, and to mature endothelial cells, which was mediated by the E-selectin/CD44 axis. ECFC proliferation and cord-like structure formation were also increased by C1P, as well as vascularization of gel plug implants loaded or not with ECFC. In a murine model of hindlimb ischemia, local administration of C1P alone promoted blood perfusion and reduced necrosis in the ischemic muscle. Additionally, the beneficial effects of ECFC infusion after ischemia were amplified by C1P pretreatment, resulting in a further and significant enhancement of leg reperfusion and muscle repair. CONCLUSIONS: Our findings suggest that C1P may have therapeutic relevance in ischemic disorders, improving tissue repair by itself, or priming ECFC angiogenic responses such as chemotaxis, adhesion, proliferation, and tubule formation, which result in a better outcome of ECFC-based therapy (Visual Overview).

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 98%

Ceramide 1-Phosphate Protects Endothelial Colony–Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo

Mena

Zubiry

Dizier

et al. 2019

ATVB

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“…Among selected species, the levels of ceramide phosphates CerP(23:0) and CerP(23:1) were significantly increased in tumor tissues as compared to adjacent normal tissues. Ceramide 1-phosphate (Cer1P) has been reported to play important role in cancer associated pathways including cell growth, survival, proliferation 17,18 , inflammation and migration 19,20 . Cer1P is synthesized through the phosphorylation of ceramide by the enzyme www.nature.com/scientificreports www.nature.com/scientificreports/ Ceramide Kinase (CERK).…”

Section: Discussionmentioning

confidence: 99%

LC-HRMS based approach to identify novel sphingolipid biomarkers in breast cancer patients

Bhadwal¹,

Dahiya²,

Shinde³

et al. 2020

Sci Rep

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perturbations in lipid metabolic pathways to meet the bioenergetic and biosynthetic requirements is a principal characteristic of cancer cells. Sphingolipids (SpLs) are the largest class of bioactive lipids associated to various aspects of tumorigenesis and have been extensively studied in cancer cell lines and experimental models. the clinical relevance of SpLs in human malignancies however is still poorly understood and needs further investigation. in the present study, we adopted a UHpLc-High resolution (orbitrap) Mass spectrometry (HRMS) approach to identify various sphingolipid species in breast cancer patients. A total of 49 SPLs falling into 6 subcategories have been identified. Further, integrating the multivariate analysis with metabolomics enabled us to identify an elevation in the levels of ceramide phosphates and sphingosine phosphates in tumor tissues as compared to adjacent normal tissues. the expression of genes involved in the synthesis of reported metabolites was also determined in local as well as TCGA cohort. A significant upregulation in the expression of CERK and SPHK1 was observed in tumor tissues in local and tcGA cohort. Sphingomyelin levels were found to be high in adjacent normal tissues. Consistent with the above findings, expression of SGMS1 in tumor tissues was downregulated in tcGA cohort only. clinical correlations of the selected metabolites and their performance as biomarkers was also evaluated. Significant ROC and positive correlation with Ki67 index highlight the diagnostic potential and clinical relevance of ceramide phosphates in breast cancer.Dysregulation of lipid homeostasis has become an established hallmark of cancer. The cancer cells exploit lipid metabolic pathways in order to fulfil their demand for energy as well as biosynthetic precursors. Aberrations in lipid metabolism thus affects numerous cellular processes such as cell growth, proliferation, differentiation and cell survival 1 . Sphingolipids (SPLs), apart from the inceptive view of being considered as mere structural components, have evolved as crucial regulators of myriads of cellular functions. The primary elements of sphingolipid metabolism such as ceramide, ceramide 1-phosphate and sphingosine 1-phosphate have recently emerged as key regulators in cancer cell growth, proliferation, survival, migration and drug resistance 2-4 . Numerous studies have described the elementary role of ceramide and sphingosine 1-phosphate rheostat in various types of cancers such as lung, breast and colon. However, these studies have provided the mechanistic details of sphingolipid metabolism in cancer cell lines and experimental models 5-7 , while their role in human malignancies is still poorly understood and needs further elucidation.Breast cancer continues to remain the most common malignancy among women worldwide 8 . The diagnosis rate of breast cancer among Indian females is as high as 25.8 per 100,000 women with a mortality rate of 12.7 per 100,000 women 9 . Despite advancement in diagnostic and therapeutic modalities, th...

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“…However, the role of C1P as an inflammatory mediator is contradictory. Thus, although C1P has been characterized as a pro-inflammatory molecule by cPLA2 activation and production of pro-inflammatory arachidonic acid metabolites [40], an anti-inflammatory effect has been documented depending on cell type [41]. Thus, C1P can be considered as a negative regulator of the LPS-dependent secretion for TNF-α [42], and additionally, exogenous C1P reduces the secretion of pro-inflammatory cytokines mediated by LPS in human peripheral blood mononuclear cells (PBMCs) and in HEK 293 cells expressing the TLR4 receptor through a reduction in NF-κB activation [43].…”

Section: Discussionmentioning

confidence: 99%

Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration

Rojas

Arán-Sekul

Cortés

et al. 2017

Toxins

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Cutaneous loxoscelism envenomation by Loxosceles spiders is characterized by the development of a dermonecrotic lesion, strong inflammatory response, the production of pro-inflammatory mediators, and leukocyte migration to the bite site. The role of phospholipase D (PLD) from Loxosceles in the recruitment and migration of monocytes to the envenomation site has not yet been described. This study reports on the expression and production profiles of cytokines and chemokines in human skin fibroblasts treated with catalytically active and inactive recombinant PLDs from Loxosceles laeta (rLlPLD) and lipid inflammatory mediators ceramide 1-phosphate (C1P) and lysophosphatidic acid (LPA), and the evaluation of their roles in monocyte migration. Recombinant rLlPLD1 (active) and rLlPLD2 (inactive) isoforms induce interleukin (IL)-6, IL-8, CXCL1/GRO-α, and CCL2/monocyte chemoattractant protein-1 (MCP-1) expression and secretion in fibroblasts. Meanwhile, C1P and LPA only exhibited a minor effect on the expression and secretion of these cytokines and chemokines. Moreover, neutralization of both enzymes with anti-rLlPLD1 antibodies completely inhibited the secretion of these cytokines and chemokines. Importantly, conditioned media from fibroblasts, treated with rLlPLDs, stimulated the transmigration of THP-1 monocytes. Our data demonstrate the direct role of PLDs in chemotactic mediator synthesis for monocytes in human skin fibroblasts and indicate that inflammatory processes play an important role during loxoscelism.

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Ceramide 1-phosphate regulates cell migration and invasion of human pancreatic cancer cells

Cited by 62 publications

References 37 publications

Ceramide 1-Phosphate Protects Endothelial Colony–Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo

Ceramide 1-Phosphate Protects Endothelial Colony–Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo

LC-HRMS based approach to identify novel sphingolipid biomarkers in breast cancer patients

Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration

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