Document Detail


Pancreatic cancer spheres are more than just aggregates of stem marker-positive cells.
MedLine Citation:
PMID:  20426768     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pancreatic cancer stem-like cells are described by membrane expression of CD24, CD44 and ESA (epithelial-specific antigen) and their capacity to grow as spheres in a serum-free medium containing well-defined growth factors. The capacity of a panel of four pancreatic cancer cell lines (PANC-1, CFPAC-1, PancTu-1 and PSN-1) to form spheres was tested. All cell lines with the exception of PancTu-1 developed spheres. Phenotypically, the sphere-growing cells showed an increased in vitro invasion capability. Both gene and protein expressions of markers of metastases [CXCR4 (CXC chemokine receptor 4), OPN (osteopontin) and CD44v6] and components of active hedgehog pathway signalling were assessed. Spheres clearly demonstrated increased expression of the above-mentioned markers when compared with their adherent counterpart. With the aim of identifying a minimum set of markers able to separate cells that have the capacity to form spheres from those incapable of forming spheres, a PCA (principal component analysis) of the multidimensional dataset was performed. Although PCA of the 'accepted' stemness genes was unable to separate sphere-forming from sphere-incapable cell lines, the addition of the 'aggressiveness' marker CD44v6 allowed a clear differentiation. Moreover, inoculation of the spheres and the adherent cells in vivo confirmed the superior aggressiveness (proliferation and metastasis) of the spheres over the adherent cells. In conclusion, the present study suggests that the sphere-growing cell population is not only composed of cells displaying classical stem membrane markers but also needs CD44v6-positive cells to successfully form spheres. Our results also emphasize the potential therapeutic importance of pathways such as CXCR4 and hedgehog for pancreatic cancer treatment.
Authors:
Margherita Gaviraghi; Patrizia Tunici; Silvia Valensin; Marco Rossi; Cinzia Giordano; Letizia Magnoni; Mario Dandrea; Licia Montagna; Rossana Ritelli; Aldo Scarpa; Annette Bakker
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Bioscience reports     Volume:  31     ISSN:  1573-4935     ISO Abbreviation:  Biosci. Rep.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-10-22     Completed Date:  2011-08-23     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  8102797     Medline TA:  Biosci Rep     Country:  United States    
Other Details:
Languages:  eng     Pagination:  45-55     Citation Subset:  IM    
Affiliation:
Department of Pathology, Policlinico GB Rossi, University of Verona, Italy. margherita.gaviraghi@tiscali.it
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MeSH Terms
Descriptor/Qualifier:
Cell Aggregation
Cell Line, Tumor
Cell Proliferation
Humans
Neoplastic Stem Cells / metabolism*,  pathology*
Pancreatic Neoplasms / metabolism*,  pathology*
Spheroids, Cellular / metabolism*,  pathology*
Tumor Markers, Biological / analysis,  metabolism*
Chemical
Reg. No./Substance:
0/Tumor Markers, Biological
Comments/Corrections

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