STEM-LIKE CELLS IN BONE SARCOMAS
First Claim
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1. A method comprising the steps of providing a sample comprising a plurality of cells from a subject having osteosarcoma;
- introducing into the cells a nucleic acid comprising an Oct-4 promoter operably linked to a reporter gene;
culturing the cells under conditions in which the reporter gene is expressed in the presence of at least one protein that activates the Oct-4 promoter;
analyzing the cells for expression of the reporter gene; and
correlating expression of the reporter gene with the presence of at least one osteosarcoma cancer stem cell.
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Abstract
Isolation and purification of stem cells from within a bulk sarcoma tumor. These cells express the marker genes of pluripotent embryonic stem cells, Stat 3, Oct 3/4, and Nanog. A subset of these cells show the surface marker of mesenchymal stem cells Stro-1, as well as express attributes of mesodermal, ectodermal, and endodermal differentiation. The isolation, purification and characterization of these stem cells now provides the ideal target for the development of highly effective therapies against tumors.
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Citations
13 Claims
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1. A method comprising the steps of providing a sample comprising a plurality of cells from a subject having osteosarcoma;
- introducing into the cells a nucleic acid comprising an Oct-4 promoter operably linked to a reporter gene;
culturing the cells under conditions in which the reporter gene is expressed in the presence of at least one protein that activates the Oct-4 promoter;
analyzing the cells for expression of the reporter gene; and
correlating expression of the reporter gene with the presence of at least one osteosarcoma cancer stem cell. - View Dependent Claims (2, 3, 4, 5, 6, 7)
- introducing into the cells a nucleic acid comprising an Oct-4 promoter operably linked to a reporter gene;
- 8. A method of inhibiting tumorigenesis in a population of cells, the method comprising contacting the population of cells with at least one agent that blocks Oct-4 promoter activity in the cells, wherein contacting the cells with the at least one agent induces at least one cell in the population of cells to differentiate.
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12. A method of identifying candidate therapeutic compounds for osteosarcoma comprising:
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culturing osteosarcoma cancer stem cells expressing at least one marker selected from;
Oct 3/4, Nanog, activated Stat-3, CXCR4, CD 133, SCA-1, Tra-1-60, CD 44, CD 73, CD 90, CD 105 and Stro-1 with at least one candidate therapeutic agent;analyzing the osteosarcoma cancer stem cells for inhibition of at least one characteristic selected from the group consisting of;
growth and migration to a tumor; andcorrelating inhibition of the at least one characteristic with the candidate therapeutic agent. - View Dependent Claims (13)
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Specification