Identification of invasive and slow-growing tumorigenic cell subsets in tumors
AssigneeThe Regents of the University of California
InventorsMandana Veiseh, Eva A. Turley, Mina J. Bissell
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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.
Claims11
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.
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.
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.
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.
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.
Dependencies are inferred from the claim text.