Use of isolated domains of type IV collagen to modify cell and tissue interaction

Abstract

The instant invention provides methods and kits for inhibiting angiogenesis, tumor growth and metastasis, and endothelial cell interactions with the extracellular matrix, involving contacting the tumor or animal tissue with at least one isolated type IV collagen NCl α chain monomer. In a specific embodiment of the invention, the isolated domain of type IV collagen comprises the NCl (α1), (α2), (α3), or (α6) chain monomer, or protein constructs having substantially the same structure as the NCl (α1), (α2), (α3), or (α6) chain monomer.

We claim:  
     
         1 . A method for inhibiting angiogenesis in an animal tissue comprising contacting the tumor or animal tissue with an amount effective to inhibit angiogenesis of a polypeptide composition comprising one or more isolated NCl α chain monomers of type IV collagen selected from the group consisting of α1, α2, α3, and α6 NCl chain monomers.  
     
     
         2 . A method for inhibiting tumor metastasis in tissue comprising contacting the tumor or tissue with an amount effective to inhibit tumor metastasis of a polypeptide composition comprising one or more isolated NCl α chain monomers of type IV collagen selected from the group consisting of α1, α2, α3, and α6 NCl chain monomers.  
     
     
         3 . A method for inhibiting tumor growth in tissue comprising contacting the tumor or tissue with an amount effective to inhibit tumor growth of a polypeptide composition comprising one or more isolated NCl α chain monomers of type IV collagen selected from the group consisting of α1, α2, α3, and α6 NCl chain monomers.  
     
     
         4 . A kit for practicing the method of  claim 1  comprising: 
 a. an amount effective to inhibit angiogenesis in an animal tissue of a polypeptide composition comprising one or more isolated NCl α a chain monomers of type IV collagen selected from the group consisting of α1, α2, α3, and α6 NCl chain monomers, and  
 b. instructions for using the amount effective of isolated NCl α chain monomers of type IV collagen to inhibit angiogenesis in an animal tissue.  
 
     
     
         5 . A kit for practicing the method of  claim 2  comprising: 
 a. an amount effective to inhibit tumor metastasis in tissue of an isolated domain of a polypeptide composition comprising one or more isolated NCl α chain monomers of type IV collagen selected from the group consisting of α1, α2, α3, and α6 NCl chain monomers and  
 b. instructions for using the amount effective of isolated NCl α chain monomers of type IV collagen to inhibit tumor metastasis in an animal tissue.  
 
     
     
         6 . A kit for practicing the method of  claim 3  comprising: 
 a. an amount effective to inhibit tumor growth in tissue of an isolated domain of a polypeptide composition comprising one or more isolated NCl α chain monomers of type IV collagen selected from the group consisting of α1, α2, α3, and α6 NCl chain monomers and  
 b. instructions for using the amount effective of isolated NCl α chain monomers of type IV collagen to inhibit tumor growth in an animal tissue.  
 
     
     
         7 . The method of  claim 1  wherein the isolated NCl α a chain monomer of type IV collagen is the α1 chain monomer.  
     
     
         8 . The method of  claim 1  wherein the isolated NCl α chain monomer of type IV collagen is the α2 chain monomer.  
     
     
         9 . The method of  claim 1  wherein the isolated NCl α chain monomer of type IV collagen is the α3 chain monomer.  
     
     
         10 . The method of  claim 1  wherein the isolated NCl α chain monomer of type IV collagen is the α6 chain monomer.  
     
     
         11 . The method of  claim 2  wherein the isolated NCl α chain monomer of type IV collagen is the α1 chain monomer.  
     
     
         12 . The method of  claim 2  wherein the isolated NCl α chain monomer of type IV collagen is the α2 chain monomer.  
     
     
         13 . The method of  claim 2  wherein the isolated NCl α chain monomer of type IV collagen is the α3 chain monomer.  
     
     
         14 . The method of  claim 2  wherein the isolated NCl α chain monomer of type IV collagen is the α6 chain monomer.  
     
     
         15 . The method of  claim 3  wherein the isolated NCl α chain monomer of type IV collagen is the α1 chain monomer.  
     
     
         16 . The method of  claim 3  wherein the isolated NCl α chain monomer of type IV collagen is the α2 chain monomer.  
     
     
         17 . The method of  claim 3  wherein the isolated NCl α chain monomer of type IV collagen is the α3 chain monomer.  
     
     
         18 . The method of  claim 3  wherein the isolated NCl α chain monomer of type IV collagen is the α6 chain monomer.  
     
     
         19 . A method for inhibiting endothelial cell interaction with the extracellular matrix in an animal tissue comprising contacting the tumor or animal tissue with an amount effective to inhibit endothelial cell interaction with the extracellular matrix of a polypeptide composition comprising one or more isolated NCl α a chain monomers of type IV collagen selected from the group consisting of α1, α2, α3, and α6 NCl chain monomers.  
     
     
         20 . A kit for practicing the method of  claim 19  comprising: 
 a. an amount effective to inhibit endothelial cell interaction with the extracellular matrix in an animal tissue of a polypeptide composition comprising one or more isolated NCl α chain monomers of type IV collagen selected from the group consisting of α1, α2, α3, and α6 NCl chain monomers, and  
 b. instructions for using the amount effective of isolated NCl α chain monomers of type IV collagen to inhibit endothelial cell interaction with the extracellular matrix in an animal tissue.  
 
     
     
         21 . The method of  claim 19  wherein the isolated NCl α chain monomer of type IV collagen is the α1 chain monomer.  
     
     
         22 . The method of  claim 19  wherein the isolated NCl α chain monomer of type IV collagen is the α2 chain monomer.  
     
     
         23 . The method of  claim 19  wherein the isolated NCl α chain monomer of type IV collagen is the α3 chain monomer.  
     
     
         24 . The method of  claim 19  wherein the isolated NCl α chain monomer of type IV collagen is the α6 chain monomer.  
     
     
         25 . A method for inhibiting tumor metastasis in tissue comprising contacting the tumor or tissue with an amount effective to inhibit tumor metastasis of a polypeptide composition comprising an isolated NCl hexamer of type IV collagen.  
     
     
         26 . A method for inhibiting tumor growth in tissue comprising contacting the tumor or tissue with an amount effective to inhibit tumor growth of a polypeptide composition comprising an isolated NCl hexamer of type IV collagen.  
     
     
         27 . A kit for practicing the method of  claim 25  comprising: 
 a. an amount effective to inhibit tumor metastasis in an animal tissue of a polypeptide composition comprising an isolated NCl hexamer of type IV collagen, and  
 b. instructions for using the amount effective of isolated NCl hexamer of type IV collagen to inhibit tumor metastasis in an animal tissue.  
 
     
     
         28 . A kit for practicing the method of  claim 26  comprising: 
 a. an amount effective to inhibit tumor growth in an animal tissue of a polypeptide composition comprising an isolated NCl hexamer of type IV collagen, and  
 b. instructions for using the amount effective of isolated NCl hexamer of type IV collagen to inhibit tumor growth in an animal tissue.  
 
     
     
         29 . A method for treating an angiogenesis-mediated disease or condition in a mammal, comprising administering to a mammal with an angiogenesis-mediated disease or condition an amount effective to inhibit angiogenesis of a polypeptide composition comprising one or more isolated NCl α chain monomers of type IV collagen selected from the group consisting of α1, α2, α3, and α6 NCl chain monomers.  
     
     
         30 . The method of  claim 29  wherein the isolated NCl α chain monomer of type IV collagen comprises the α1 NCl chain monomer.  
     
     
         31 . The method of  claim 29  wherein the isolated NCl α chain monomer of type IV collagen comprises the α2 NCl chain monomer.  
     
     
         32 . The method of  claim 29  wherein the isolated NCl α chain monomer of type IV collagen comprises the α3 NCl chain monomer.  
     
     
         33 . The method of  claim 29  wherein the isolated NCl α chain monomer of type IV collagen comprises the α6 NCl chain monomer.  
     
     
         34 . The method of claim  45  wherein the angiogenesis-mediated disease or condition is selected from the group consisting of solid and blood-borne tumors, diabetic retinopathy, rheumatoid arthritis, retinal neovascularization, choroidal neovascularization, macular degeneration, corneal neovascularization, retinopathy of prematurity, corneal graft rejection, neovascular glaucoma, retrolental fibroplasia, epidemic keratoconjunctivitis, Vitamin A deficiency, contact lens overwear, atopic keratitis, superior limbic keratitis, pterygium keratitis sicca, sogrens, acne rosacea, phylectenulosis, syphilis, Mycobacteria infections, lipid degeneration, chemical bums, bacterial ulcers, fungal ulcers, Herpes simplex infections, Herpes zoster infections, protozoan infections, Kaposi's sarcoma, Mooren ulcer, Terrien's marginal degeneration, marginal keratolysis, traum, systemic lupus, polyarteritis, Wegeners sarcoidosis, scleritis, Steven's Johnson disease, radial keratotomy, sickle cell anemia, sarcoid, pseudoxanthoma elasticum, Pagets disease, vein occlusion, artery occulsion, carotid obstructive disease, chronic uveitis, chronic vitritis, Lyme's disease, Eales disease, Bechets disease, myopia, optic pits, Stargarts disease, pars planitis, chronic retinal detachment, hyperviscosity syndromes, toxoplasmosis, post-laser complications, abnormal proliferation of fibrovascular tissue, hemangiomas, Osler-Weber-Rendu, acquired immune deficiency syndrome, ocular neovascular disease, osteoarthritis, chronic inflammation, Crohn's disease, ulceritive colitis, psoriasis, atherosclerosis, and pemphigoid.