Collecting ovarian cancer stem cells from ovarian cancer cells

Patent metadata

Field	Value
Publication number	US-9289492-B2
Application number	US-66913608-A
Country	US
Kind code	B2
Filing date	Jul 17, 2008
Priority date	Jul 17, 2007
Publication date	Mar 22, 2016
Grant date	Mar 22, 2016

Abstract

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.

First claim

The invention claimed is:

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).

Assignees

• Donahoe Patricia K
• Szotek Paul P
• Maclaughlin David T
• Preffer Frederic
• Pieretti-Vanmarcke Rafael
• Dombkowski David Michael
• Gen Hospital Corp

Inventors

• Donahoe Patricia K
• Szotek Paul P
• Maclaughlin David T
• Preffer Frederic
• Pieretti-Vanmarcke Rafael
• Dombkowski David Michael

Classifications

• G01N33/57545

  of the ovaries · CPC title

• C12N2501/998

  Proteins not provided for elsewhere · CPC title

• G01N2800/44

  Multiple drug resistance · CPC title

• A61K31/00

  Medicinal preparations containing organic active ingredients · CPC title

• C12N2503/00

  Use of cells in diagnostics · CPC title