Compositions And Methods For Treating And Diagnosing Pancreatic Cancer

• US 20080261244A1
• Filed: 01/24/2008
• Published: 10/23/2008
• Est. Priority Date: 01/24/2007
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Simeone, Diane M., Wicha, Max S., Clarke, Michael F.
• Granted Patent: US 8,148,147 B2
• Time in Patent Office: Days
• US Class Current: 435/7.23
• CPC Class Codes: A01K 2267/0331 Animal model for proliferative diseases
• CPC Class Codes: C12N 5/0695 Stem cells; Progenitor cells; Precursor cells

Abstract

The present invention relates to the field of oncology and provides novel compositions and methods for diagnosing and treating pancreatic cancer. In particular, the present invention provides pancreatic cancer stem cells useful for the study, diagnosis, and treatment of solid tumors.

Claims

1. An isolated population of cancer stem cells that are:

a) tumorigenic;

b) CD44+;

c) CD24+ and,

d) ESA+.

2. The isolated population of cancer stem cells of claim 1, wherein the population comprises at least 75% cancer stem cells and less than 25% non-tumorigenic tumor cells.

3. The isolated population of cancer stem cells of claim 1, wherein the cancer stem cells are pancreatic cancer stem cells.

4. The isolated population of cancer stem cells of claim 1, wherein the cancer stem cells are obtained from a tumor of epithelial origin.

5. The isolated population of cancer stem cells of claim 1, wherein the cancer stem cells have upregulated expression of SHH.

6. The isolated population of cancer stem cells of claim 1, wherein the cancer stem cells:

are enriched at least two-fold compared to unfractionated non-tumorigenic tumor cells.

7. A method of obtaining from a tumor an isolated population of cancer stem cells comprising:

a) contacting a mixture of tumor cells from a tumor with reagents against CD44, CD24, and ESA, and

b) positively selecting for cells that are CD44+, CD24+, and ESA+.

8. A method of identifying the presence of pancreatic cancer stem cells in a subject suspected of having cancer, wherein the method comprises:

(a) obtaining a biological sample from the subject;

(b) dissociating cells of the sample;

(c) contacting the dissociated cells with a first reagent that binds CD44, a second reagent that binds CD24, and a third reagent that binds ESA; and

(d) detecting cancer stem cells that bind to the first, second, and third reagents.

9. The method of claim 8, wherein the first reagent, second reagent or third reagent is an antibody.

10. The method of claim 8, wherein the detection step is performed by flow cytometry, fluorescence activated cell sorting, panning, affinity column separation, or magnetic selection.

11. A method of treating a patient with pancreatic cancer comprising;

administering a SHH inhibitor to said patient such that the number of pancreatic stem cells expressing CD44, CD24 and ESA is reduced or eliminated in the subject.