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

摘要

The present disclosure provides innovative methodology and related compositions and kits for preventing and treating various diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, by using an inhibitor of processed forms of lysyl oxidase or lysyl oxidase-like proteins, an inhibitor of LOX and an inhibitor of a LOXL, or a synergistic combination of an inhibitor of LOX or LOXL combined with other therapeutic agents. Also provided are innovative methods for selecting agents that prevent or inhibit tumor invasion, angiogenesis and metastasis, by contacting cells that are in an epithelial-mesenchymal transition (EMT) state with a candidate agent and detecting a change in the EMT state of the cells. Methods and related compositions and kits for diagnosing or monitoring various diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, by using molecules or agents that specifically recognize processed forms of LOX or LOXL are also provided. Also provided herein are methods and related compositions, medical devices, systems and kits for preventing or treating various diseases and conditions associated with fibrosis with compositions comprising inhibitors of LOX or LOXL. Such diseases or conditions include pathological cardiovascular conditions and diseases such as hypertension, hypertensive heart disease, myocardial infarction, atherosclerosis, and restenosis, liver fibrosis, kidney fibrosis, lung fibrosis, dermal scaring, keloid formation, and Alzheimer's disease.