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[Cancer Research 65, 5506-5511, July 1, 2005]
© 2005 American Association for Cancer Research

Priority Reports

Isolation and In vitro Propagation of Tumorigenic Breast Cancer Cells with Stem/Progenitor Cell Properties

Dario Ponti1, Aurora Costa1, Nadia Zaffaroni1, Graziella Pratesi1, Giovanna Petrangolini1, Danila Coradini1, Silvana Pilotti2, Marco A. Pierotti1,3 and Maria Grazia Daidone1

1 Department of Experimental Oncology and Laboratories and 2 Department of Pathology, Istituto Nazionale Tumori; and 3 Cancer Genetic Unit, The Firc Institute of Molecular Oncology Foundation, Milan, Italy

Requests for reprints: Maria Grazia Daidone, Department of Experimental Oncology and Laboratories, Unit #10, Istituto Nazionale Tumori, Via Venezian, 1, Milan 20133, Italy. Phone: 39-02-2390-2238; E-mail: mariagrazia.daidone{at}istitutotumori.mi.it.

Breast cancer–initiating cells have been recently identified in breast carcinoma as CD44+/CD24–/low cells, which exclusively retain tumorigenic activity and display stem cell–like properties. However, at present, direct evidence that breast cancer–initiating cells can be propagated in vitro is still lacking. We report here the isolation and in vitro propagation of breast cancer–initiating cells from three breast cancer lesions and from an established breast carcinoma cell line. Our breast carcinoma–derived cultures encompassed undifferentiated cells capable of self-renewal, extensive proliferation as clonal nonadherent spherical clusters, and differentiation along different mammary epithelial lineages (ductal and myoepithelial). Interestingly, cultured cells were CD44+/CD24– and Cx43–, overexpressed neoangiogenic and cytoprotective factors, expressed the putative stem cell marker Oct-4, and gave rise to new tumors when as few as 103 cells were injected into the mammary fat pad of SCID mice. Long-term cultures of breast tumorigenic cells with stem/progenitor cell properties represent a suitable in vitro model to study breast cancer–initiating cells and to develop therapeutic strategies aimed at eradicating the tumorigenic subpopulation within breast cancer.




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