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Characterization of stem cell-like cancer cells in immune-competent mice

Academic Article
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Overview

authors

  • Kruger, J. A.
  • Kaplan, C. D.
  • Luo, Y. P.
  • Zhou, H.
  • Markowitz, D.
  • Xiang, R.
  • Reisfeld, Ralph

publication date

  • December 2006

journal

  • Blood  Journal

abstract

  • Recently, the cancer stem cell hypothesis has gained significant recognition as the descriptor of tumorigenesis. Although previous studies relied on transplanting human or rat tumor cells into immunecompromised mice, our study used the Hoechst 33342 dye-based side population (SP) technique to isolate and transplant stem cell-like cancer cells (SCLCCs) from the 4T1 and NXS2 murine carcinoma cell lines into the immune-competent microenvironment of syngeneic mice. 4T1 cells displayed an SP of 2% with a Sca-1(high)c-Kit(-)CD45(-) phenotype, whereas NXS2 cells contained an SP of 0.2% with a Sca-1(high)CD24(high)c-Kit(-)CD45(-)GD (high)(2) phenotype. Reverse transcription-polymerase chain reaction (RT-PCR) further revealed up-regulation in SP cells of ABCG2, Sca-1, Wnt-1, and TGF-beta2. Additionally, 4T1 and NXS2 SP cells exhibited increased resistance to chemotherapy, and 4T1 SP cells also showed an increased ability to efflux doxorubicin, which correlated with a selective increase in the percentage of SP cells found in the tumors of doxorubicin-treated mice. Most importantly, SP cells showed a markedly higher repopulation and tumorigenic potential in vivo, which correlated with an increased number of cells in the SP compartment of SP-derived tumors. Taken together, these results show that we successfully characterized SCLCCs from 2 murine carcinoma cell lines in the immune-competent microenvironment of syngeneic mice.

subject areas

  • Animals
  • Antibiotics, Antineoplastic
  • Benzimidazoles
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Doxorubicin
  • Drug Resistance, Neoplasm
  • Female
  • Fluorescent Dyes
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplastic Stem Cells
  • Rats
  • Up-Regulation
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Identity

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2066-05-024687

PubMed ID

  • 16912222
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Additional Document Info

start page

  • 3906

end page

  • 3912

volume

  • 108

issue

  • 12

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