Pancreatic ductal adenocarcinoma cell secreted extracellular vesicles containing ceramide-1-phosphate promote pancreatic cancer stem cell motility

Kuc, Norbert; Doermann, Allison; Shirey, Carolyn M.; Lee, Daniel D.; Lowe, Chinn-Woan; Awasthi, Niranjan; Schwarz, Roderich E.; Stahelin, Robert V.; Schwarz, Margaret A.

doi:10.1016/j.bcp.2018.09.017

Cited by 22 publications

(19 citation statements)

References 34 publications

(40 reference statements)

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“…Experimental data support this notion. An increased ceramide conversion into ceramide-1-phosphate (C1P) was shown to play a role in cancer stem cell migration, facilitating PDAC tumor growth [ 36 ]; however, C1P inhibition reduced the motility of PDAC cell lines [ 37 ]. Other lipid metabolites, such as cholesterol, were described to regulate PDAC differentiation.…”

Section: Discussionmentioning

confidence: 99%

Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma

Mahajan

Alnatsha

et al. 2021

Cells

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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Developing biomarkers for early detection and chemotherapeutic response prediction is crucial to improve the dismal prognosis of PDAC patients. However, molecular cancer signatures based on transcriptome analysis do not reflect intratumoral heterogeneity. To explore a more accurate stratification of PDAC phenotypes in an easily accessible matrix, plasma metabolome analysis using MxP® Global Profiling and MxP® Lipidomics was performed in 361 PDAC patients. We identified three metabolic PDAC subtypes associated with distinct complex lipid patterns. Subtype 1 was associated with reduced ceramide levels and a strong enrichment of triacylglycerols. Subtype 2 demonstrated increased abundance of ceramides, sphingomyelin and other complex sphingolipids, whereas subtype 3 showed decreased levels of sphingolipid metabolites in plasma. Pathway enrichment analysis revealed that sphingolipid-related pathways differ most among subtypes. Weighted correlation network analysis (WGCNA) implied PDAC subtypes differed in their metabolic programs. Interestingly, a reduced expression among related pathway genes in tumor tissue was associated with the lowest survival rate. However, our metabolic PDAC subtypes did not show any correlation to the described molecular PDAC subtypes. Our findings pave the way for further studies investigating sphingolipids metabolisms in PDAC.

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Section: Discussionmentioning

confidence: 99%

Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma

Mahajan

Alnatsha

et al. 2021

Cells

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“…Although it is not highly permeable, C1P can cross the cell membrane to be released to the extracellular milieu, where it is found in concentrations as high as 20 μM ( 22 , 135 , 136 ). Existence of a C1P-specific transporter and its secretion in vesicles have been reported ( 134 , 137 ). C1P is a second messenger as well as an extracellular ligand, activating multiple signaling pathways including PI3K, ERK/MAPK, Jun N-terminal kinase (JNK), cytosolic phospholipase A2, NF-κB, and glycogen synthase kinase 3 (GSK3) ( 138 ).…”

Section: C1p: a Complementing Performermentioning

confidence: 99%

Sphingolipids as critical players in retinal physiology and pathology

Simón

Basu

Qaladize

et al. 2021

Journal of Lipid Research

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Sphingolipids have emerged as bioactive lipids involved in the regulation of many physiological and pathological processes. In the retina, they have been established to participate in numerous processes, such as neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Dysregulation of sphingolipids is, therefore, crucial in the onset and progression of retinal diseases. This review examines the involvement of sphingolipids in retinal physiology and diseases. Ceramide (Cer) emerges as a common mediator of inflammation and death of neuronal and retinal pigment epithelium cells in animal models of retinopathies such as glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa. Sphingosine-1-phosphate (S1P) has opposite roles, preventing photoreceptor and ganglion cell degeneration but also promoting inflammation, fibrosis, and neovascularization in AMD, glaucoma, and pro-fibrotic disorders. Alterations in Cer, S1P, and ceramide-1-phosphate may also contribute to uveitis. Notably, use of inhibitors that either prevent Cer increase or modulate S1P signaling, such as Myriocin, desipramine, and Fingolimod (FTY720), preserves neuronal viability and retinal function. These findings underscore the relevance of alterations in the sphingolipid metabolic network in the etiology of multiple retinopathies and highlight the potential of modulating their metabolism for the design of novel therapeutic approaches.

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“…In pancreatic ductal adenocarcinoma (PDAC), exosomal IncRNA Sox2ot promotes EMT and stem cell-like properties by regulating Sox2 expression. 208 Kuc et al 209 reported that PDAC-derived exosomes promoted pancreatic CSCs motility. In addition, in prostate cancer, exosomes secreted by tumor cells under hypoxic conditions promoted the stemness and aggressiveness of naive prostate cancer cells.…”

Section: The Cross Talk Between Evs and Cscs Nichementioning

confidence: 99%

The key roles of cancer stem cell-derived extracellular vesicles

Zhang

Yarden

et al. 2021

Sig Transduct Target Ther

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Cancer stem cells (CSCs), the subpopulation of cancer cells, have the capability of proliferation, self-renewal, and differentiation. The presence of CSCs is a key factor leading to tumor progression and metastasis. Extracellular vesicles (EVs) are nano-sized particles released by different kinds of cells and have the capacity to deliver certain cargoes, such as nucleic acids, proteins, and lipids, which have been recognized as a vital mediator in cell-to-cell communication. Recently, more and more studies have reported that EVs shed by CSCs make a significant contribution to tumor progression. CSCs-derived EVs are involved in tumor resistance, metastasis, angiogenesis, as well as the maintenance of stemness phenotype and tumor immunosuppression microenvironment. Here, we summarized the molecular mechanism by which CSCs-derived EVs in tumor progression. We believed that the fully understanding of the roles of CSCs-derived EVs in tumor development will definitely provide new ideas for CSCs-based therapeutic strategies.

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Pancreatic ductal adenocarcinoma cell secreted extracellular vesicles containing ceramide-1-phosphate promote pancreatic cancer stem cell motility

Cited by 22 publications

References 34 publications

Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma

Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma

Sphingolipids as critical players in retinal physiology and pathology

The key roles of cancer stem cell-derived extracellular vesicles

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