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Title: Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis

Cancer stem cells are a distinct cellular population that is believed to be responsible for tumor initiation and maintenance. Recent data suggest that solid tumors also contain another type of stem cells, the mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs), which contribute to the formation of tumor-associated stroma. The Hoechst 33342 efflux assay has proved useful to identify a rare cellular fraction, named Side Population (SP), enriched in cells with stem-like properties. Using this assay, we identified SP cells in a prostate cancer xenograft containing human prostate cancer cells and mouse stromal cells. The SP isolation, subculture and sequential sorting allowed the generation of single-cell-derived clones of murine origin that were recognized as MSC by their morphology, plastic adherence, proliferative potential, adipogenic and osteogenic differentiation ability and immunophenotype (CD45{sup -}, CD81{sup +} and Sca-1{sup +}). We also demonstrated that SP clonal cells secrete transforming growth factor {beta}1 (TGF-{beta}1) and that their inhibition reduces proliferation and accelerates differentiation. These results reveal the existence of SP cells in the stroma of a cancer xenograft, and provide evidence supporting their MSC nature and the role of TGF-{beta}1 in maintaining their proliferation and undifferentiated status. Our data also reveal the usefulness ofmore » the SP assay to identify and isolate MSC cells from carcinomas.« less
Authors:
 [1] ;  [2] ;  [1] ;  [2] ;  [2] ; ; ;  [1] ;  [2] ;  [1] ;  [2] ;  [2] ;  [3] ;  [4] ;  [5] ;  [2] ;  [1] ;  [2] ;  [1] ;  [2]
  1. Institut de Recerca Hospital Vall d'Hebron, Barcelona (Spain)
  2. (Spain)
  3. (ICREA), Barcelona (Spain)
  4. Institut Curie, Paris (France)
  5. Universitat Autonoma de Barcelona, Barcelona (Spain)
Publication Date:
OSTI Identifier:
22209831
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 315; Journal Issue: 17; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOMAS; CELL PROLIFERATION; GROWTH FACTORS; INHIBITION; MICE; MORPHOLOGY; PROSTATE; STEM CELLS