Extracellular Collagenases and the Endocytic Receptor, Urokinase Plasminogen Activator Receptor-associated Protein/Endo180, Cooperate in Fibroblast-mediated Collagen Degradation

摘要: The collagens of the extracellular matrix are most abundant structural proteins in mammalian body. In tissue remodeling and invasive growth malignant tumors, constitute an important barrier, consequently, turnover collagen is a rate-limiting process these events. A recently discovered route with importance for tumor involves intracellular degradation governed by receptor, urokinase plasminogen activator receptor-associated protein (uPARAP or Endo180). interplay between this mechanism collagenolysis not known. report, we demonstrate existence new, composite breakdown pathway. Thus, fibroblast-mediated proceeds preferentially as sequential which followed uPARAP/Endo180-mediated endocytosis large fragments. First, show that has been pre-cleaved collagenase taken up much more efficiently than intact, native uPARAP/Endo180-positive cells. Second, preference acquisition gelatin-like structure collagen, occurring upon collagenase-mediated cleavage under conditions. Third, uPARAP/Endo180-deficient fibroblasts on leads to substantial accumulation well defined fragments, whereas, wild-type possess ability direct organized complete sequence comprising both initial cleavage, endocytic uptake, collagen.