H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen.

TLDR

Type IV collagenase has three domains—an amino‑terminal and carboxyl‑terminal domain homologous to interstitial collagenase and stromelysin, and a middle domain of 175 residues with fibronectin‑like repeats. The authors propose to designate the TBE‑1 secreted protease as type IV collagenase because it initiates pepsin‑resistant degradation of type IV collagen. TBE‑1 cells secrete a 72‑kDa latent metalloprotease that, once activated, preferentially cleaves type IV collagen and other extracellular matrix proteins, is identical to gelatinase from normal skin and fibroblasts, and represents the third member of a newly recognized gene family of secreted extracellular matrix metalloproteases.

Abstract

H-ras-transformed human bronchial epithelial cells (TBE-1) secrete a single major extracellular matrix metalloprotease which is not found in the normal parental cells. The enzyme is secreted in a latent form of 72 kDa, which can be activated to catalyze the cleavage of the basement membrane macromolecule type IV collagen. The substrates in their order of preference are: gelatin, type IV collagen, type V collagen, fibronectin, and type VII collagen; but the enzyme does not cleave the interstitial collagens or laminin. This protease is identical to gelatinase isolated from normal human skin explants, normal human skin fibroblasts, and SV40-transformed human lung fibroblasts. Based on its ability to initiate the degradation of type IV collagen in a pepsin-resistant portion of the molecule, it will be referred to as type IV collagenase. This enzyme is most likely the human analog of type IV collagenase detected in several rodent tumors, which has the same molecular mass and has been linked to their metastatic potential. Type IV collagenase consists of three domains. Two of them, the amino-terminal domain and the carboxyl-terminal domain, are homologous to interstitial collagenase and human and rat stromelysin. The middle domain, of 175 residues, is organized into three 58-residue head-to-tail repeats which are homologous to the type II motif of the collagen-binding domain of fibronectin. Type IV collagenase represents the third member of a newly recognized gene family coding for secreted extracellular matrix metalloproteases, which includes interstitial fibroblast collagenase and stromelysin.