Blog
About

23
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment.

      Nature medicine

      Transplantation, Heterologous, Transfection, Transcription, Genetic, genetics, RNA, Small Interfering, pharmacology, Polyenes, prevention & control, pathology, Neoplasm Metastasis, Mice, Nude, Mice, Lactones, Humans, Female, Cell Line, Tumor, Breast Neoplasms, Antibodies, Monoclonal, Animals, Aminopropionitrile, metabolism, drug effects, antagonists & inhibitors, Amino Acid Oxidoreductases

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          We have identified a new role for the matrix enzyme lysyl oxidase-like-2 (LOXL2) in the creation and maintenance of the pathologic microenvironment of cancer and fibrotic disease. Our analysis of biopsies from human tumors and fibrotic lung and liver tissues revealed an increase in LOXL2 in disease-associated stroma and limited expression in healthy tissues. Targeting LOXL2 with an inhibitory monoclonal antibody (AB0023) was efficacious in both primary and metastatic xenograft models of cancer, as well as in liver and lung fibrosis models. Inhibition of LOXL2 resulted in a marked reduction in activated fibroblasts, desmoplasia and endothelial cells, decreased production of growth factors and cytokines and decreased transforming growth factor-beta (TGF-beta) pathway signaling. AB0023 outperformed the small-molecule lysyl oxidase inhibitor beta-aminoproprionitrile. The efficacy and safety of LOXL2-specific AB0023 represents a new therapeutic approach with broad applicability in oncologic and fibrotic diseases.

          Related collections

          Author and article information

          Journal
          20818376
          10.1038/nm.2208

          Comments

          Comment on this article