Extracellular matrix compositions for the treatment of cancer

Abstract

The present invention is directed to methods of inhibiting cancer cell growth or proliferation by contacting the cancer cell with an extracellular matrix (ECM) composition. Also provided are methods of delivering a chemotherapeutic agent to a cancer cell by contacting a cancer cell with an extracellular matrix composition containing a chemotherapeutic agent. Also provided are compositions containing ECM and a chemotherapeutic agent.

What is claimed is: 
     
         1 . A method of inhibiting metastatic cancer cell growth or proliferation, comprising:
 a) culturing fibroblast cells on microbeads under hypoxic conditions of 1-5% oxygen to produce a hypoxic ECM; and   b) contacting the metastatic cancer cell with the hypoxic ECM;   thereby inhibiting metastatic cancer cell growth or proliferation.   
     
     
         2 . The method of  claim 1 , wherein the cancer cell is from a cancer selected from the group consisting of melanoma, glioma, and adenocarcinoma, bladder cancer, bone cancer, cancer of the bone marrow, brain cancer, spinal cancer, breast cancer, cervical cancer, gall bladder cancer, cancer of the ganglia, cancer of the gastrointestinal tract, stomach cancer, colon cancer, cancer of the heart, kidney cancer, liver cancer, lung cancer, muscle cancer, ovarian cancer, pancreatic cancer, parathyroid cancer, cancer of the penis, prostate cancer, cancer of the salivary glands, skin cancer, cancer of the spleen, cancer of the testis, thymus cancer, thyroid cancer, or uterine cancer. 
     
     
         3 . The method of  claim 1 , wherein, wherein the hypoxic ECM composition has a soluble fraction. 
     
     
         4 . The method of  claim 1 , wherein the hypoxic ECM composition has a non-soluble fraction. 
     
     
         5 . The method of  claim 1 , wherein the hypoxic ECM composition is a combination of a soluble and non-soluble fraction. 
     
     
         6 . The method of  claim 3 , wherein the soluble fraction comprises a molecular weight fraction comprising molecules having a molecular weight less than 30,000 Daltons. 
     
     
         7 . The method of  claim 6 , wherein the molecules have a molecular weight less than 5,000 Daltons. 
     
     
         8 . The method of  claim 1 , further comprising administrating to the subject an anti-inflammatory agent, antihistamines, chemotherapeutic agent, immunomodulator, therapeutic antibody or a protein kinase inhibitor. 
     
     
         9 . The method of  claim 8 , wherein the chemotherapeutic agent is an alkaloid; covalent DNA-binding agent; noncovalent DNA-binding agent; antimetabolite; enzyme; hormone; platinum compound; monoclonal antibody conjugated with anticancer a drug, toxin, and/or radionuclide; biological response modifier; hematopoietic growth factor; inhibitor of angiogenesis; DNA cross-linking agent; topoisomerase I inhibitor; or microtubule inhibitor. 
     
     
         10 . The method of  claim 8 , wherein the chemotherapeutic agent is selected from the group consisting of 2-Chlorodeoxyadenosine, 2′-Deoxycoformycin, 2′-Deoxycoformycin, 5-fluorouracil, 5-fluorodeoxyuridine, 4-dimethoxy-daunomycin, 11-deoxydaunorubicin, 13-deoxydaunorubicin, adriamycin-14-benzoate, adriamycin-14-octanoate, adriamycin-14-naphthaleneacetate, 6-Mercaptopurine, 6-Thioguanine, acyclovir, amsacrine, anastrozole, asparaginase, azathioprine, busulfan, camptothecin, canbusil, carboplatin, carminomycin, carmustine, chlorambucil, chlorodeoxyadenosine, cisplatin, cyclophosphamide, cytarabine, dactinomycin, dacarbazine, daunorubicin, doxorubicin, docetaxel, doxorubicin, epirubicin, etoposide, fludarabine, flutamide, hydroxymethylmelamine, idarubicin, ifosphamide, isirinotecan, lomustine, lovastatin, mechlorethamine, melphalan, methotrexate, mithoxanthrone, mitocycin, oxalaplatin, semustine, thiotepa, tamoxifen, taxol, taxotere; teniposide, thioguanine, topetecan, vincristine, vinblastine, and vindesine. 
     
     
         11 . The method of  claim 1 , wherein the contacting the metastatic cancer cells with the hypoxic ECM is performed after a surgical resection. 
     
     
         12 . The method of  claim 1 , wherein the hypoxic ECM further comprises a chemotherapeutic agent and/or an immunomodulatory agent. 
     
     
         13 . The method of  claim 12 , wherein the chemotherapeutic agent is selected from the group consisting of 2-Chlorodeoxyadenosine, 2′-Deoxycoformycin, 2′-Deoxycoformycin, 5-fluorouracil, 5-fluorodeoxyuridine, 4-dimethoxy-daunomycin, 11-deoxydaunorubicin, 13-deoxydaunorubicin, adriamycin-14-benzoate, adriamycin-14-octanoate, adriamycin-14-naphthaleneacetate, 6-Mercaptopurine, 6-Thioguanine, azathioprine, acyclovir, amsacrine, anastrozole, asparaginase, busulfan, camptothecin, canbusil, carboplatin, carminomycin, carmustine, chlorambucil, chlorodeoxyadenosine, cisplatin, cyclophosphamide, cytarabine, dactinomycin, dacarbazine, daunorubicin, doxorubicin, docetaxel, doxorubicin, epirubicin, etoposide, fludarabine, flutamide, hydroxymethylmelamine, idarubicin, ifosphamide, isirinotecan, lomustine, lovastatin, mechlorethamine, melphalan, methotrexate, mithoxanthrone, mitocycin, oxalaplatin, semustine, thiotepa, tamoxifen, taxol, taxotere; teniposide, thioguanine, topetecan, vincristine, vinblastine, and vindesine. 
     
     
         14 . The method of  claim 1 , wherein the fibroblast cells are human. 
     
     
         15 . The method of  claim 1 , wherein the fibroblast cells are adult, fetal, neonatal or embryonic fibroblast cells. 
     
     
         16 . The method of  claim 1 , wherein the metastatic cancer cell is contacted in vivo.