Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties.
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 10(3) 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.
Department of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, Milan, Italy.
Dario
D
Ponti
Aurora
A
Costa
Nadia
N
Zaffaroni
Graziella
G
Pratesi
Giovanna
G
Petrangolini
Danila
D
Coradini
Silvana
S
Pilotti
Marco A
MA
Pierotti
Maria Grazia
MG
Daidone
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D051927:CD24 Antigen; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D016513:Mice, SCID; D011230:Precancerous Conditions / Q000473:pathology; D013234:Stem Cells / Q000276:immunology / Q000473:pathology*
D015703:Antigens, CD; D051927:CD24 Antigen; C497889:CD24 protein, human; C497890:Cd24a protein, mouse; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins