# US 2013/0157285 A1 · Identification of invasive and slow-growing tumorigenic cell subsets in tumors

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- Number: US 2013/0157285 A1
- Document ID: US20130157285A1
- Status: Published application
- Kind: A1
- Application number: 13/651,381
- Filed: 2012-10-12
- Published: 2013-06-20
- Earliest claimed: 2011-10-12
- Assignees: The Regents of the University of California
- Inventors: Mandana Veiseh; Eva A. Turley; Mina J. Bissell
- Web page: https://patentgrep.com/patent/US20130157285A1

## CPC

- C12Q 1/02: involving viable microorganisms
- G01N 33/57515: of the breast
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

HA-based functional probes and a multiplexed targeting strategy for detection and isolation of invasive subpopulations in breast cancer cell lines. Methods for using HA metabolism for profiling and sorting breast cancer heterogeneity. As such, HA-based functional probes have appropriate targeting capacity and safety profiles for development as imaging and therapeutic agents for following repair and neoplastic disease processes such as breast cancer.

## Claims

### Claim 1

A method for isolating a cell, comprising: (a) providing a polydisperse (5-500 kDa Molecular weight range) labeled hyaluronan probe (HA probe); (b) contacting a cell with the labeled HA probe; (c) detecting high HA uptake in said cell, wherein high HA uptake is at least 100 fold differences in HA binding and/or uptake and metabolism by said cell, which indicates said cell is highly invasive, slow-growing and able to invade the lymphovasculature, and (d) isolating said cell having high HA uptake.

### Claim 2 (depends on 1)

The method of claim 1, wherein said cell having a genotype of CD44+/CD24−/RHAMM+/HAhigh.

### Claim 3

A method of prognosis of a cancer patient comprising the steps of: (a) obtaining a tissue biopsy from a patient; (b) labeling cells from said biopsy with a labeled hyaluronan probe; (c) sorting said cells based on high or negative/low uptake of the labeled hyaluronan probe; (d) determining if any cells highly uptake the labeled hyaluronan probe, wherein high uptake of the labeled hyaluronan probe by cells indicates those cells are highly invasive and able to invade the lymphovasculature.

### Claim 4 (depends on 3)

The method of claim 3, wherein the biopsy is obtained from an epithelial tissue.

### Claim 5 (depends on 4)

The method of claim 4, wherein the epithelial tissue is breast tissue.

### Claim 6

A method of inhibiting cancer cell metastasis, the method comprising: (a) providing a polydisperse (5-500 kDa Molecular weight range) labeled hyaluronan probe (HA probe) attached to a therapeutic; (b) administering the labeled HA probe-therapeutic to a subject; (c) detecting high HA uptake in a cell, wherein high HA uptake is at least 100 fold differences in HA binding and/or uptake and metabolism by said cell, which indicates said cell is invasive, slow-growing and able to invade the lymphovasculature.

### Claim 7 (depends on 6)

The method of claim 6 wherein the therapeutic is an antibody, a small molecule, a mimetic, a peptide, a siRNA, an antisense oligo, or an aptamer.

### Claim 8

A probe for targeting triple negative breast cancer cells and delivering therapy to those cells, said probe comprising a polydisperse (5-500 kDa Molecular weight range) hyaluronan probe (HA probe) attached to a therapeutic.

### Claim 9

A probe for identifying tumorigenic cell populations, comprising a HA-binding targeting component and an imaging component, wherein said HA-binding targeting component specifically binds to the CD44+/CD24−/RHAMM+/HAhigh cells, and wherein said imaging component is a detectable label.

### Claim 10 (depends on 9)

The probe of claim 9 wherein the ligand is hyaluronan, a hyaluronan fragment, or any chemical composition that is an HA mimetic.

### Claim 11 (depends on 9)

The probe of claim 9 wherein the detectable label is a metal or fluorescent label.