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Document Type and Number:
Japanese Patent JP2005511754
Kind Code:
Human breast tumors contain hetrogeneous cancer cells. using an animal xenograft model in which human breast cancer cells were grown in immunocompromised mice we found that only a small minority of breast cancer cells had capacity to form new tumors. The ability to form new tumors was not a slochastic property, rather certain populations of cancer cells were depleted for the ability to form new tumors, while other populations were enriched for the ability to form new tumors. Tumorigenic cells could be distinguished from non-tumorigenic cancer cells based on surface marker expression. We prospectively identified and isolated the tumorigenic cells as CD4430CD24-/lowLINEAGE A few as 100 cells from this population were able to form tumors the animal xenograft model, while tens of thousands of cells from non-tumorigenic populations failed to form tumors. The tumorigenic cells could be serially passaged, each time generating new tumors containing and expanded numbers of CD44+CD24 Lineage tumorigenic cells as well as phenotypically mixed populations of non-tumorigenic cancer cells. This is reminiscent of the ability of normal stem cells to self-renew and differentiate. The expression of potential therapeutic targets also differed between the tumorigenic and non-tumorigenic populations. Notch activation promoted the survival of the tumorigenic cells, and a blocking antibody against Notch 4 induced tumorigenic breast cancer cells to undergo apoptosis.

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Clark Michael F.
Witcha Max S.
Al-haj mohmad
Application Number:
Publication Date:
April 28, 2005
Filing Date:
December 06, 2002
Export Citation:
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International Classes:
G01N33/574; A01K67/027; A61K31/00; A61K35/76; A61K38/00; A61K38/17; A61K39/395; A61K45/00; A61K47/48; A61P15/00; A61P35/00; C07K16/18; C07K16/28; C07K16/30; A61K39/00; (IPC1-7): A61K45/00; A61K35/76; A61K38/00; A61K39/395; A61P15/00; A61P35/00; G01N33/574
Attorney, Agent or Firm:
Hatsushi Shimizu
Kazunori Hashimoto
Koichi Niimi