Isolation, gene expression, and chemotherapeutic resistance of motile cancer cells
AssigneeAlbert Einstein College of Medicine of Yeshiva University
InventorJohn S. Condeelis
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Abstract
Methods of isolating motile cells of interest from an animal tissue is provided. Also provided are methods of determining mRNA or protein expression of a gene in motile cells of interest from an animal tissue. Additionally, methods of determining whether a cancer in a tissue of a mammal is likely to metastasize are provided. Methods are also provided for inhibiting metastasis of a cancer in a tissue of a mammal. Further provided are methods of determining resistance of a motile cancer cell population in an animal tissue to a chemotherapeutic agent.
Claims14
A method of determining whether a cancer in a tissue of a mammal is likely to metastasize, the method comprising
- obtaining a microneedle or capillary filled with a porous matrix comprising a chemotactic factor;
- inserting the microneedle or capillary into the tissue for a time sufficient for motile cells to migrate into the porous matrix;
- expelling the porous matrix with motile cells from the microneedle or capillary;
- combining the porous matrix with microbeads, where the microbeads comprise a binding partner to a surface marker present on macrophages from the tissue;
- removing the microbeads and bound macrophages;
- and
- obtaining a gene expression profile of motile tumor cells remaining after removal of the microbeads,
- wherein the gene that is profiled includes one or more of collagen type III α1, G-protein coupled receptor 26, Zip code binding protein 1, fibroblast growth factor receptor 1, Arp2/3 p16 subunit, tight junction protein 2, member Ras oncogene family, and epidermal growth factor receptor, and
- wherein downregulation of expression of one or more of collagen type III α1, G-protein coupled receptor 26, Zip code binding protein 1, or fibroblast growth factor receptor 1 compared to expression in non-metastatic tumor cells, and/or upregulation of expression of one or more of Arp2/3 p16 subunit, tight junction protein 2, member Ras oncogene family or epidermal growth factor receptor compared to expression in non-metastatic tumor cells indicates that the profiled tumor cells are metastatic tumor cells and that the cancer is likely to metastasize.
A method of identifying metastatic tumor cells from a tumor, the method comprising:
- isolating motile tumor cells from the tumor;
- obtaining a gene expression profile of the motile tumor cells, wherein the genes that are profiled include all of collagen type III α1, G-protein coupled receptor 26, Zip code binding protein 1, fibroblast growth factor receptor 1, Arp2/3 p16 subunit, tight junction protein 2, member Ras oncogene family, and epidermal growth factor receptor;
- and
- comparing the expression of collagen type III α1, G-protein coupled receptor 26, Zip code binding protein 1, fibroblast growth factor receptor 1, Arp2/3 p16 subunit, tight junction protein 2, member Ras oncogene family and epidermal growth factor receptor in the profiled tumor cells to their expression in non-metastatic tumor cells, wherein downregulation of expression of one or more of collagen type III α1, G-protein coupled receptor 26, Zip code binding protein 1, or fibroblast growth factor receptor 1 compared to expression in non-metastatic tumor cells, and/or upregulation of expression of one or more of Arp2/3 p16 subunit, tight junction protein 2, member Ras oncogene family or epidermal growth factor receptor compared to expression in non-metastatic tumor cells indicates that the profiled tumor cells are metastatic tumor cells, thereby identifying said profiled tumor cells as metastatic tumor cells.
Dependencies are inferred from the claim text.