skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Abstract

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
Journal Name:
Experimental Cell Research
Additional Journal Information:
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); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOMAS; CELL PROLIFERATION; GROWTH FACTORS; INHIBITION; MICE; MORPHOLOGY; PROSTATE; STEM CELLS

Citation Formats

Santamaria-Martinez, Albert, Universitat de Barcelona, Barcelona, Barquinero, Jordi, Universitat Autonoma de Barcelona, Barcelona, Banc de Sang i Teixits, Barcelona, Barbosa-Desongles, Anna, Hurtado, Antoni, Pinos, Tomas, Universitat Autonoma de Barcelona, Barcelona, Seoane, Joan, Universitat Autonoma de Barcelona, Barcelona, Medical Oncology program, Vall d'Hebron Institute of Oncology, Barcelona, Institucio Catalana de Recerca i Estudis Avancats, Poupon, Marie-France, Morote, Joan, Servei d'Urologia. Hospital Vall d'Hebron, Barcelona, Reventos, Jaume, Universitat Autonoma de Barcelona, Barcelona, Munell, Francina, E-mail: fmunell@ir.vhebron.net, and Universitat Autonoma de Barcelona, Barcelona. Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis. United States: N. p., 2009. Web. doi:10.1016/J.YEXCR.2009.05.007.
Santamaria-Martinez, Albert, Universitat de Barcelona, Barcelona, Barquinero, Jordi, Universitat Autonoma de Barcelona, Barcelona, Banc de Sang i Teixits, Barcelona, Barbosa-Desongles, Anna, Hurtado, Antoni, Pinos, Tomas, Universitat Autonoma de Barcelona, Barcelona, Seoane, Joan, Universitat Autonoma de Barcelona, Barcelona, Medical Oncology program, Vall d'Hebron Institute of Oncology, Barcelona, Institucio Catalana de Recerca i Estudis Avancats, Poupon, Marie-France, Morote, Joan, Servei d'Urologia. Hospital Vall d'Hebron, Barcelona, Reventos, Jaume, Universitat Autonoma de Barcelona, Barcelona, Munell, Francina, E-mail: fmunell@ir.vhebron.net, & Universitat Autonoma de Barcelona, Barcelona. Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis. United States. doi:10.1016/J.YEXCR.2009.05.007.
Santamaria-Martinez, Albert, Universitat de Barcelona, Barcelona, Barquinero, Jordi, Universitat Autonoma de Barcelona, Barcelona, Banc de Sang i Teixits, Barcelona, Barbosa-Desongles, Anna, Hurtado, Antoni, Pinos, Tomas, Universitat Autonoma de Barcelona, Barcelona, Seoane, Joan, Universitat Autonoma de Barcelona, Barcelona, Medical Oncology program, Vall d'Hebron Institute of Oncology, Barcelona, Institucio Catalana de Recerca i Estudis Avancats, Poupon, Marie-France, Morote, Joan, Servei d'Urologia. Hospital Vall d'Hebron, Barcelona, Reventos, Jaume, Universitat Autonoma de Barcelona, Barcelona, Munell, Francina, E-mail: fmunell@ir.vhebron.net, and Universitat Autonoma de Barcelona, Barcelona. Thu . "Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis". United States. doi:10.1016/J.YEXCR.2009.05.007.
@article{osti_22209831,
title = {Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis},
author = {Santamaria-Martinez, Albert and Universitat de Barcelona, Barcelona and Barquinero, Jordi and Universitat Autonoma de Barcelona, Barcelona and Banc de Sang i Teixits, Barcelona and Barbosa-Desongles, Anna and Hurtado, Antoni and Pinos, Tomas and Universitat Autonoma de Barcelona, Barcelona and Seoane, Joan and Universitat Autonoma de Barcelona, Barcelona and Medical Oncology program, Vall d'Hebron Institute of Oncology, Barcelona and Institucio Catalana de Recerca i Estudis Avancats and Poupon, Marie-France and Morote, Joan and Servei d'Urologia. Hospital Vall d'Hebron, Barcelona and Reventos, Jaume and Universitat Autonoma de Barcelona, Barcelona and Munell, Francina, E-mail: fmunell@ir.vhebron.net and Universitat Autonoma de Barcelona, Barcelona},
abstractNote = {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 of the SP assay to identify and isolate MSC cells from carcinomas.},
doi = {10.1016/J.YEXCR.2009.05.007},
journal = {Experimental Cell Research},
issn = {0014-4827},
number = 17,
volume = 315,
place = {United States},
year = {2009},
month = {10}
}