Isolation and use of solid tumor stem cells

US8357491B2 · kind B2 · utility

Assignee

• THE REGENTS OF THE UNIVERSITY OF MICHIGAN · US

Inventors

• Michael F. Clarke · Ann Arbor, US
• Sean Morrison · Ann Arbor, US
• Max S. Wicha · Ann Arbor, US
• Muhammad Al-Hajj · Cambridge, US

Key dates

• Filing date: Dec 28, 2010
• Grant date: Jan 22, 2013
• Expiry date: Dec 28, 2030

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2503/00
• WIPO field: Measurement
• WIPO sector: Instruments

Abstract

A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise to both 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.