Document Detail


Altered intracellular calcium fluxes in pancreatic cancer induced diabetes mellitus: Relevance of the S100A8 N-terminal peptide (NT-S100A8).
MedLine Citation:
PMID:  20717964     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  226     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-11-30     Completed Date:  2011-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  456-68     Citation Subset:  IM    
Copyright Information:
© 2010 Wiley-Liss, Inc.
Affiliation:
Department of Laboratory Medicine, University of Padua, Padua, Italy.
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MeSH Terms
Descriptor/Qualifier:
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:
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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