Isolation and use of solid tumor stem cells

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 5/00 (2006.01) C12N 5/095 (2010.01) A01K 67/027 (2006.01) A61K 35/12 (2006.01) A61K 38/00 (2006.01) A61K 39/00 (2006.01) A61K 39/395 (2006.01) C12N 15/09 (2006.01) C12N 15/11 (2006.01) C12Q 1/00 (2006.01) C12Q 1/02 (2006.01) C12Q 1/68 (2006.01) C40B 40/02 (2006.01) C40B 40/06 (2006.01) C40B 40/10 (2006.01) G01N 33/53 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2417909

A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. We have developed a xenograft model in which we have been able to establish tumors from primary tumors via injection of tumors in the mammary gland of severely immunodeficient mice. These xenograft assay have allowed us to do biological and molecular assays to characterize clonogenic solid tumor stem cells. We have also developed evidence that strongly implicates the Notch pathway, especially Notch 4, as playing a central pathway in carcinogenesis.

L'invention concerne un faible pourcentage des cellules d'une tumeur solide établie, présentant des propriétés de cellules souches. Ces cellules souches de tumeurs solides génèrent d'autres cellules souches tumorales ainsi que la majorité des cellules tumorales ayant perdu la capacité de proliférer de manière extensive et de générer de nouvelles tumeurs. L'hétérogénéité de la tumeur solide reflète la présence d'une descendance de cellules tumorales née d'une cellule souche de la tumeur solide. Un modèle de xénogreffe a été mis au point dans lequel on a pu établir des tumeurs à partir de tumeurs primaires par l'injection de tumeurs dans la glande mammaire de souris sévèrement immunodéprimées. L'analyse de cette xénogreffe a permis de procéder à des analyses biologiques et moléculaires permettant de caractériser les cellules souches clonogéniques de la tumeur solide. On a ainsi pu obtenir des preuves impliquant fortement la voie de Notch, en particulier Notch 4, comme voie centrale de carcinogenèse.

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