| Altered intracellular calcium fluxes in pancreatic cancer induced diabetes mellitus: Relevance of the S100A8 N-terminal peptide (NT-S100A8). | |
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MedLine Citation:
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PMID: 20717964 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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After isolating NT-S100A8 from pancreatic cancer (PC) tissue of diabetic patients, we verified whether this peptide alters PC cell growth and invasion and/or insulin release and [Ca(2+)](i) oscillations of insulin secreting cells and/or insulin signaling. BxPC3, Capan1, MiaPaCa2, Panc1 (PC cell lines) cell growth, and invasion were assessed in the absence or presence of 50, 200, and 500 nM NT-S100A8. In NT-S100A8 stimulated β-TC6 (insulinoma cell line) culture medium, insulin and [Ca(2+)] were measured at 2, 3, 5, 10, 15, 30, and 60 min, and [Ca(2+)](i) oscillations were monitored (epifluorescence) for 3 min. Five hundred nanomolars NT-S100A8 stimulated BxPC3 cell growth only and dose dependently reduced MiaPaCa2 and Panc1 invasion. Five hundred nanomolars NT-S100A8 induced a rapid insulin release and enhanced β-TC6 [Ca(2+)](i) oscillations after both one (F = 6.05, P < 0.01) and 2 min (F = 7.42, P < 0.01). In the presence of NT-S100A8, [Ca(2+)] in β-TC6 culture medium significantly decreased with respect to control cells (F = 6.3, P < 0.01). NT-S100A8 did not counteract insulin induced phosphorylation of the insulin receptor, Akt and IκB-α, but it independently activated Akt and NF-κB signaling in PC cells. In conclusion, NT-S100A8 exerts a mild effect on PC cell growth, while it reduces PC cell invasion, possibly by Akt and NF-κB signaling, NT-S100A8 enhances [Ca(2+)](i) oscillations and insulin release, probably by inducing Ca(2+) influx from the extracellular space, but it does not interfere with insulin signaling. |
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Authors:
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Daniela Basso; Eliana Greco; Andrea Padoan; Paola Fogar; Michele Scorzeto; Elisa Fadi; Dania Bozzato; Stefania Moz; Filippo Navaglia; Carlo-Federico Zambon; Roberta Seraglia; Eugenio De Carlo; Anna Valerio; Carlo Reggiani; Sergio Pedrazzoli; Mario Plebani |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular physiology Volume: 226 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2010-11-30 Completed Date: 2011-01-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 456-68 Citation Subset: IM |
Copyright Information:
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© 2010 Wiley-Liss, Inc. |
Affiliation:
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Department of Laboratory Medicine, University of Padua, Padua, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium / metabolism* Calgranulin A / genetics, metabolism* Cell Line, Tumor Diabetes Mellitus / etiology*, metabolism Humans Insulin / secretion Islets of Langerhans / drug effects, metabolism Pancreatic Neoplasms / complications*, metabolism, pathology, physiopathology Peptides / genetics, metabolism*, pharmacology Rats Signal Transduction / physiology |
| Chemical | |
Reg. No./Substance:
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0/Calgranulin A; 0/Peptides; 11061-68-0/Insulin; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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