Lysyl oxidase-like protein localizes to sites of de novo fibrinogenesis in fibrosis and in the early stromal reaction of ductal breast carcinomas

Abstract

Lysyl oxidase (LO) initiates the first step in the crosslinking of collagens and elastin and has also been shown to function as a tumor suppressor. The purpose of the present work was to determine whether the products of a newly described LO-like gene (LOXL) that encodes a close homolog of LO, the LO-like (LOL) protein, is associated with extracellular matrix remodeling during fibrotic disorders. Specific antibody against LOL identified proteins of approximately 30, 42, 52 and 68 kd in various cells and in bovine aorta. These proteins were immunochemically distinct from the recombinant LO expressed by fibroblasts and from the bovine aorta LO. The LO gene (LOX) and LOXL were transiently up-regulated at early stages of liver granuloma development in Schistosoma mansoni-infected mice, although the peak of LOL mRNA synthesis preceded that of LO. LOL protein and LO were colocalized at sites of fibrogenesis in human lung fibrosis and in the stromal reaction of bronchiolo-alveolar carcinomas and of in situ ductal breast tumors. In conclusion, the LOL protein was identified as a secreted protein and localized in the extracellular matrix in active fibrotic diseases and in the early stromal reaction of breast cancer.