Methods and compositions for treatment and diagnosis of fibrosis, tumor invasion, angiogenesis, and metastasis

Abstract

Provided are methodology, compositions and kits to prevent and treat diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, using processed lysyl oxidase or lysyl oxidase-like protein inhibitors, LOX inhibitors and LOXL inhibitors, or synergistic combinations of such inhibitors with therapeutic agents. Provided are methods for selecting tumor invasion, angiogenesis and metastasis inhibiting agents, by contacting cells in EMT states with candidate agents and detecting changes in such states; and methods, compositions, and kits for diagnosing or monitoring diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, using molecules or agents specifically recognizing processed LOX or LOXL. Provided are methods, compositions, medical devices, systems and kits for preventing or treating diseases and conditions associated with fibrosis, including pathological cardiovascular conditions and diseases, e.g., hypertension, hypertensive heart disease, myocardial infarction, atherosclerosis, restenosis, liver fibrosis, kidney fibrosis, lung fibrosis, dermal scaring, keloid formation, and Alzheimer's disease, with LOX or LOXL inhibitors.

What is claimed is: 
     
         1 . A method for diagnosing cancer metastasis in a subject, comprising:
 assessing active LOX or LOXL levels or activity in the blood,   wherein a change in active LOX or LOXL levels or activity in the blood in comparison with a reference sample indicates the presence of metastatic tumor growth.   
     
     
         2 . The method of  claim 1 , wherein active LOX or LOXL levels or activities in the blood is lower than those in a reference sample indicates the presence or increase of cancer metastasis. 
     
     
         3 . A method for diagnosing cancer metastasis in a subject having a tumor, comprising:
 assessing active LOX or LOXL levels or activity in the tumor,   wherein a change in active LOX or LOXL levels or activity in the tumor in comparison with a reference sample indicates the presence of metastatic tumor growth.   
     
     
         4 . The method of  claim 1  or  3 , wherein active LOX or LOXL levels or activities in the tumor is higher than those in a reference sample indicates the presence or increase of cancer metastasis. 
     
     
         5 . The method of  claim 1  or  3 , wherein the step of assessing includes assessing the levels of the active LOX or LOXL using an antibody that binds to the active LOX or LOXL. 
     
     
         6 . The method of  claim 1  or  3 , wherein the step of assessing includes assessing the levels of the active LOX or LOXL using an antibody that binds to the active LOX, LOXL2 or LOXL4. 
     
     
         7 . The method of  claim 1  or  3 , wherein assessing comprises assessing the levels of the active LOX or LOXL using an antibody that binds to both active LOX and active LOXL2. 
     
     
         8 . The method of  claim 1  or  3 , wherein the active LOX or LOXL is a mature form of LOX or LOXL after proteolytic processing of the preproprotein.