Isolation and use of solid tumor stem cells
A small percentage of cells within an established 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.
1 - 185 . (canceled)
186 . A cellular composition obtained from a solid tumor comprising at least 75% solid tumor stem cells and 25% or less solid tumor cells wherein:
the solid tumor stem cells are tumorigenic; and,
the solid tumor cells are non-tumorigenic.
187 . The cellular composition of claim 186 wherein the solid tumor stem cells and solid tumor cells are obtained from a solid tumor selected from the group consisting of colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, cervical cancer, lung carcinoma, small cell lung carcinoma, bladder carcinoma, glioma, astrocytoma, and melanoma.
188 . The cellular composition of claim 186 wherein the solid tumor stem cells and solid tumor cells are obtained from a human head and neck tumor.
189 . The cellular composition of claim 186 wherein the solid tumor stem cells and solid tumor cells are obtained from a human pancreatic tumor.
190 . The cellular composition of claim 186 wherein the solid tumor stem cells and solid tumor cells are obtained from a human pulmonary tumor.
191 . The cellular composition of claim 186 wherein the solid tumor stem cells and solid tumor cells are obtained from a human ovarian tumor.
192 . The cellular composition of claim 186 wherein the solid tumor stem cells and solid tumor cells are obtained from a human liver tumor.
193 . The cellular composition of claim 186 wherein the solid tumor stem cells and solid tumor cells are obtained from a human kidney tumor.
194 . The cellular composition of claim 186 wherein the solid tumor stem cells and solid tumor cells are obtained from a human colon tumor.
195 . The cellular composition of claim 186 wherein the solid tumor stem cells are human breast cancer solid tumor stem cells.
196 . The cellular composition of claim 186 wherein the cellular composition is in a culture medium.
197 . The cellular composition of claim 196 wherein the culture medium comprises a notch ligand.
198 . The cellular composition of claim 186 wherein the cellular composition has been treated to inhibit tumorigenesis.
199 . The cellular composition of claim 186 wherein the solid tumor stem cells and solid tumor cells are obtained from bodily fluids.
200 . A cellular composition obtained from a solid tumor comprising at least 75% solid tumor stem cells and 25% or less solid tumor cells wherein:
the solid tumor stem cells are tumorigenic by serial injection of said solid tumor stem cells into a host animal; and,
the solid tumor cells are non-tumorigenic by serial injection of said solid tumor cells into the host animal.
201 . A cellular composition obtained from a solid tumor comprising at least 90% solid tumor stem cells and less than 10% solid tumor cells wherein:
the solid tumor stem cells are tumorigenic; and,
the solid tumor cells are non-tumorigenic.
202 . The cellular composition of claim 201 wherein the solid tumor stem cells and solid tumor cells are obtained from a human tumor selected from the group consisting of colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, cervical cancer, lung carcinoma, small cell lung carcinoma, bladder carcinoma, glioma, astrocytoma, or melanoma.
203 . The cellular composition of claim 201 wherein the solid tumor stem cells and solid tumor cells are obtained from a human head and neck tumor.
204 . The cellular composition of claim 201 wherein the solid tumor stem cells and solid tumor cells are obtained from a human pancreatic tumor.
205 . The cellular composition of claim 201 wherein the solid tumor stem cells and solid tumor cells are obtained from a human pulmonary tumor.
206 . The cellular composition of claim 201 wherein the solid tumor stem cells and solid tumor cells are obtained from a human ovarian tumor.
207 . The cellular composition of claim 201 wherein the solid tumor stem cells and solid tumor cells are obtained from a human liver tumor.
208 . The cellular composition of claim 201 wherein the solid tumor stem cells and solid tumor cells are obtained from a human kidney tumor.
209 . The cellular composition of claim 201 wherein the solid tumor stem cells and solid tumor cells are obtained from a human colon tumor.
210 . The cellular composition of claim 201 wherein the solid tumor stem cells are human breast cancer solid tumor stem cells.
211 . The cellular composition of claim 201 wherein the cellular composition is in a culture medium.
212 . The cellular composition of claim 201 wherein the culture medium comprises a notch ligand.
213 . The cellular composition of claim 201 wherein the cellular composition has been treated to inhibit tumorigenesis.
214 . The cellular composition of claim 201 wherein the solid tumor stem cells and solid tumor cells are obtained from bodily fluids.
215 . A cellular composition comprising at least 90% solid tumor stem cells and less than 10% solid tumor cells wherein:
the solid tumor stem cells are tumorigenic by serial injection of said solid tumor stem cells into a host animal; and,
the solid tumor cells are non-tumorigenic by serial injection of said solid tumor cells into the host animal.
216 . A cellular composition obtained from a solid tumor comprising solid tumor stem cells and solid tumor cells wherein the solid tumor stem cells are enriched two-fold and are tumorigenic by serial injection of said solid tumor stem cells into a host animal.
217 . The cellular composition of claim 216 wherein the solid tumor stem cells are enriched at least five-fold.
218 . The cellular composition of claim 216 wherein the solid tumor stem cells are enriched at least ten-fold.
219 . The cellular composition of claim 216 wherein the solid tumor stem cells and solid tumor cells are obtained from bodily fluids.