Collecting ovarian cancer stem cells from ovarian cancer cells
The present invention relates to compositions and methods for treating, characterizing and diagnosing ovarian cancer. In particular, the present invention provides methods for treating and/or preventing ovarian cancer in a subject by administering to the subject an effective amount of Mullerian Inhibiting substance and/or an effective amount of an agent that inhibits BCRP1. The present invention further provides methods to identify and/or enrich for populations of ovarian cancer stem cells and populations of somatic ovarian stem cells, in particular, enrichment for populations of coelomic somatic ovarian stem cells, subcoelomic/stromal somatic ovarian stem cells and periphilar medullary somatic ovarian stem cells. The present invention also provides somatic ovarian stem cell markers and ovarian cancer stem cell markers, as well as methods to identify agents which selectively inhibit the proliferation of ovarian cancer stem cells as compared to somatic ovarian stem cells.
1. A method for collecting a population of ovarian cancer stem cells, the method comprising
(i) contacting a biopsy tissue sample comprising a population of ovarian cancer cells with an anti-EpCam, an anti-cytokeratin-8 and an anti-β-catenin antibody, antibody derivative or fragment thereof;
(ii) separating the ovarian cancer cells that are positive for binding the combination of anti-EpCam, anti-cytokeratin-8, and anti-β-catenin antibodies, from the ovarian cancer cells that do not bind all three of the antibodies;
(iii) collecting the ovarian cancer cells that are positive for the binding of the combination of anti-EpCam, anti-cytokeratin-8, and anti-β-catenin antibodies, wherein the isolated ovarian cancer cells comprises ovarian cancer stem cells.
2. The method of claim 1 , further comprising measuring the expression of breast cancer-resistance protein 1 (BCRP1) and/or the ability of the ovarian cells to efflux a lipophilic dye, and collecting the population of ovarian cells which are positive for BCRP1 expression and/or the ability to efflux a lipophic dye.
3. The method of claim 1 , wherein the biopsy tissue sample comprises ovarian cancer cells.
4. The method of claim 3 , wherein the ovarian cancer cells are selected from the group comprising, vulvar epidermal carcinoma cells, cervical carcinoma cells, endometrial adenocarcinoma cells and ovarian adenocarcinoma cells.
5. The method of claim 1 , wherein the biopsy tissue sample is obtained from a human subject.
6. The method of claim 1 , wherein the biopsy tissue sample is obtained from a mammal.
7. The method of claim 1 , wherein the ovarian cancer stem cell population has multi-drug resistance sensitivity.
8. The method of claim 7 , wherein the ovarian cancer stem cell population is resistant to paclitaxel, cisplatin, doxorubicin.
9. The method of claim 7 , wherein the ovarian cancer stem cell population is sensitive to a BCRP1 inhibitor.
10. The method of claim 8 , wherein the BCRP1 inhibitor is verapamil.
11. The method of claim 7 , wherein the ovarian cancer stem cell population is sensitive to recombinant mullerian inhibiting substance (MIS).