Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US6984522

Title:Isolation and use of solid tumor stem cells
Inventors:Clarke, Michael F.; Ann Arbor, MI, USA
Morrison, Sean J.; Ann Arbor, MI, USA
Wicha, Max S.; Ann Arbor, MI, USA
Al-Hajj, Muhammad; Ann Arbor, MI, USA
Summary:Described herein is a method for the isolation of solid tumor stem cells expressing the cell surface marker CD44. It has been shown that a small percentage of cells within an established solid tumor have the properties of stem cells, such that these solid tumor stem cells give rise both to more tumor stem cells and to the majority of the cells in the tumor that have lost the capacity for extensive proliferation and the ability to develop new tumors. This invention relates to principles by which solid tumor heterogeneity has been found to reflect the presence of tumor cell progeny arising from a solid tumor stem cell. Further disclosed are methods of determining the ability of compounds to inhibit tumorigenesis in solid tumor stem cells of epithelial origin. Therapeutic applications are included for the identification of new anti-cancer drug targets, and for factors influencing tumor stem cell proliferation. This invention represents a continuation of other applications filed by the same assignee and inventors.
Abstract: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. The solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells. 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. Xenograft tumors have been established from mastectomy specimens of breast cancer patients. Furthermore, in the three tumors that we have tested, we have been able to make single-cell suspensions and transfer the tumors serially through immunocompromised mice. These improvements in the 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. Antibodies against Notch4 reduced tumor cell proliferation and survival.
US Patent Website:Click Here for Full Text of Patent
Title Number:US6984522
Application Number:US2001000920517
Date Filed:01/08/2001
Date Published:10/01/2006
Assignee:Regents of the University of Michigan, Ann Arbor, MI, USA


 
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