Compositions and methods for treating and diagnosing cancer
AssigneeThe Regents of the University of Michigan
InventorsMichael F. Clarke, Tim Hoey, Xinhao Wang, Scott Dylla, Austin Gurney, Piero Dalerba, Grace Chen, Mark Prince
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Abstract
The present invention relates to compositions and methods for characterizing, treating and diagnosing cancer. In particular, the present invention provides a cancer stem cell profile, as well as novel stem cell cancer markers useful for the diagnosis, characterization, prognosis and treatment of cancer and in particular the targeting of solid tumor stem cells.
Claims17
An isolated population of cancer stem cells obtained from a tumor of epithelial origin, wherein the population comprises at least 75% cancer stem cells and less than 25% non-tumorigenic tumor cells, wherein the cancer stem cells:
- are tumorigenic;
- and,
- express elevated levels of one or more of PTGFRN, CD166, CD164, CD82, TGFBR1, MET, EFNB2, ITGA6, TDGF1, HBEGF, ABCC4, ABCD3, TDE2, ITGB1, TNFRSF21, CD81, CD9, KIAA1324, CEACAM6, FZD6, FZD7, BMPR1A, JAG1, ITGAV, NOTCH2, SOX4, HES1, HES6, ATOH1, CDH1, EPHB2, MYB, MYC, SOX9, PCGF1, PCGF4, PCGF5, ALDH1A1, and STRAP, or reduced levels of one or both of TCF4 or VIM relative to the non-tumorigenic tumor cells.
6-10. (canceled)
A method for obtaining from a tumor a cellular composition comprising cancer stem cells and non-tumorigenic tumor cells, wherein at least 75% are tumorigenic stem cells and 25% or less are non-tumorigenic tumor cells, said method comprising:
- (a) obtaining a dissociated mixture of tumor cells from a tumor of epithelial origin;
- (b) separating the mixture of tumor cells into a first fraction comprising at least 75% cancer stem cells and 25% or less non-tumorigenic tumor cells and a second fraction of tumor cells depleted of cancer stem cells wherein the separating is by contacting the mixture with reagents against CD44 and ESA;
- and
- (c) demonstrating the first fraction to be tumorigenic by serial injection into a first host animal and the second fraction to be non-tumorigenic by serial injection into a second host animal.
A method for enriching a population of cancer stem cells from a tumor of epithelial origin wherein the enriched population comprises 75% cancer stem cells and 25% or less non-tumorigenic tumor cells, said method comprising:
- (a) obtaining a dissociated mixture of tumor cells from a tumor of epithelial origin;
- (b) contacting the mixture of tumor cells with reagents against CD44 and ESA;
- (c) selecting a first fraction of cancer stem cells by their binding to the reagents and a second fraction of colon tumor cells depleted of colon cancer stem cells;
- and
- (d) demonstrating the first fraction to be tumorigenic by serial injection of the colon tumor stem cells into a host animal and the second fraction to be non-tumorigenic by serial injection into the host animal.
-68. (canceled)
Dependencies are inferred from the claim text.