Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like subpopulation within the MCF7 breast cancer cell line

Authors

  • Massimiliano Cariati,

    1. Department of Academic Oncology, King's College London and Guy's & St Thomas' NHS Foundation Trust, United Kingdom
    2. Cancer Genomics Program, Department of Oncology, University of Cambridge, Cambridge, United Kingdom
    3. Department of Surgery, University of Cambridge, Cambridge, United Kingdom
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  • Ali Naderi,

    1. Cancer Genomics Program, Department of Oncology, University of Cambridge, Cambridge, United Kingdom
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  • John P. Brown,

    1. Cancer Genomics Program, Department of Oncology, University of Cambridge, Cambridge, United Kingdom
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  • Matthew J. Smalley,

    1. The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom
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  • Sarah E. Pinder,

    1. Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
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  • Carlos Caldas,

    1. Cancer Genomics Program, Department of Oncology, University of Cambridge, Cambridge, United Kingdom
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  • Anand D. Purushotham

    Corresponding author
    1. Department of Academic Oncology, King's College London and Guy's & St Thomas' NHS Foundation Trust, United Kingdom
    • Department of Academic Oncology, 3rd Floor Thomas Guy House, Guy's Hospital, St Thomas Street, London SE1 9RT, UK===

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Abstract

The identification of mammary epithelial stem cells raises the hypothesis that these cells may be crucial in the pathogenesis of breast cancer. To further support this, a highly tumourigenic sub-population of cancer cells has recently been identified in primary and metastatic breast cancer samples. In this study, a sub-population of cells displaying features normally attributed to stem cells was identified within the breast cancer cell line MCF-7. This sub-population is capable of growth in anchorage-independent conditions as spherical organoids, displays resistance to proapoptotic agents and significantly greater tumourigenicity than its parental line, with as few as 1,000 cells able to form tumours in immunodeficient mice. Cells within this sub-population can be enriched by serial passages in anchorage-independence, and are characterized by over-expression of the adhesion molecule α6-integrin. Alpha-6 integrin proves to be required for the growth and survival of these cells, as the knockdown of ITGA6 causes mammosphere-derived cells to lose their ability to grow as mammospheres and abrogates their tumourigenicity in mice. These findings support the existence of a highly tumourigenic sub-population in breast cancer cells. Furthermore, it shows α6-integrin as a potential therapeutic target aimed at tumour-generating subsets of breast cancer cells. © 2007 Wiley-Liss, Inc.

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