Open Access

The CD49d+/high subpopulation from isolated human breast sarcoma spheres possesses tumor-initiating ability

  • Authors:
    • Kyung-Min Lee
    • Wonshik Han
    • Jong Bin Kim
    • Incheol Shin
    • Eunyoung Ko
    • In Ae Park
    • Dong Sup Lee
    • Kuenhee Oh
    • Dong-Young Noh
  • View Affiliations

  • Published online on: December 8, 2011     https://doi.org/10.3892/ijo.2011.1289
  • Pages: 665-672
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Abstract

Primary breast sarcomas (PBSs) that arise from mammary stroma are very rare, highly aggressive and therapy- resistant tumors with a heterogeneous phenotype. In this study, we sought to identify tumor-initiating cells (TICs) in PBSs and to describe their features. We isolated long-term self-renewing sarcospheres (designated NDY-1) from primary breast carcinosarcoma tissue (sarcoma component >95%) using the anchorage-independent culture method. NDY-1 spheres expressed various mesenchymal cell markers, and their tumorigenic potential was markedly reduced in adherent culture conditions, compared to spheres. Screening for integrins revealed a marked decrease in CD49d expression in adherent culture conditions of NDY-1. The CD49d+/high subpopulation sorted from NDY-1 spheres displayed higher cell viability and sphere-forming ability than CD49d-/low population in vitro. Moreover, the CD49d+/high population displayed high tumor initiating ability in limiting dilution transplantation to NOD/SCID mice, and the xenotransplanted CD49d+/high population recapitulated the complexity of the original primary tumors. Greater doxorubicin resistance was exhibited by the CD49d+/high population, compared with the CD49d-/low population. Thus, our results collectively demonstrate that CD49d+/high cells from sarcospheres display enhanced sphere-forming, drug resistance and tumor-initiating abilities. To our knowledge, this is the first study to identify TICs from breast sarcoma.

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March 2012
Volume 40 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Lee K, Han W, Kim JB, Shin I, Ko E, Park IA, Lee DS, Oh K and Noh D: The CD49d+/high subpopulation from isolated human breast sarcoma spheres possesses tumor-initiating ability. Int J Oncol 40: 665-672, 2012
APA
Lee, K., Han, W., Kim, J.B., Shin, I., Ko, E., Park, I.A. ... Noh, D. (2012). The CD49d+/high subpopulation from isolated human breast sarcoma spheres possesses tumor-initiating ability. International Journal of Oncology, 40, 665-672. https://doi.org/10.3892/ijo.2011.1289
MLA
Lee, K., Han, W., Kim, J. B., Shin, I., Ko, E., Park, I. A., Lee, D. S., Oh, K., Noh, D."The CD49d+/high subpopulation from isolated human breast sarcoma spheres possesses tumor-initiating ability". International Journal of Oncology 40.3 (2012): 665-672.
Chicago
Lee, K., Han, W., Kim, J. B., Shin, I., Ko, E., Park, I. A., Lee, D. S., Oh, K., Noh, D."The CD49d+/high subpopulation from isolated human breast sarcoma spheres possesses tumor-initiating ability". International Journal of Oncology 40, no. 3 (2012): 665-672. https://doi.org/10.3892/ijo.2011.1289