Regulation of matrilysin expression in cells of squamous cell carcinoma by E-cadherin-mediated cell-cell contact

Abstract

A critical attribute of invasive carcinomas is their ability to degrade components of the extracellular matrix, a process achieved by the matrix metalloproteases. In the human squamous cell carcinoma cell line II-4, mRNA and protein expression of the matrix metalloprotease matrilysin was observed to be significantly higher in confluent than in log-phase growth conditions. The purpose of this study was to determine the basis for this switch in constitutive matrilysin expression. Conditioned medium from confluent cultures did not induce matrilysin in log-phase cultures, nor did conditioned medium from log-phase cultures repress matrilysin expression in confluent cultures. Thus, matrilysin expression was found not to be controlled by factors autocrine product. Matrilysin protein levels were, however, found to be directly correlated to the degree of cell-cell contact. Incubation of confluent cultures in 30 microM calcium medium, which disrupts E-cadherin-mediated cell-cell contact, was subsequently found to inhibit matrilysin expression, as did treatment with an anti-E-cadherin-neutralizing antibody. These results demonstrate that the degree of cell-cell contact mediated by the E-cadherin cell-adhesion molecule can influence constitutive metalloprotease expression levels in cultured squamous cell carcinoma cells.

EGF induces the expression of matrilysin in the human prostate adenocarcinoma cell line, LNCaP

“…Another level of regulation is that total proteinase activity is modulated by specific tissue inhibitors of metalloproteinases (TIMPs), which complex with MMPs and keep them in an inactive state. MMPs are regulated at the transcriptional level by growth factors, tumor promoters, oncogenes, and adhesion molecules [34,35]. The coordinated induction of several MMPs by these agents is due to the similarity in the 5' flanking region of their promoters.…”

Comprehensive Analysis of Matrix Metalloproteinase and Tissue Inhibitor Expression in Pancreatic Cancer

“…Loss of E-cadherin expression in a transgenic mouse model of pancreatic ␤-cell carcinogenesis (Rip1Tag2) coincides with the transition from well-differentiated adenoma to invasive carcinoma (92). Curiously, it has also been demonstrated that E-cadherin stimulates expression of MMP-7 through the wnt-signaling pathway (93).…”

The metalloproteinase matrilysin is a target of β-catenin transactivation in intestinal tumors

“…In most carcinomas, MMPs are expressed in stromal cells and many have been shown to be regulated by interaction with ECM through integrins (Pilcher et al, 1997;Damsky et al, 1997). In contrast, matrilysin expression is found at high levels in well-dierentiated epithelial cells (Wilson and Matrisian, 1998) and has been shown to be tightly regulated by E-cadherin mediated cell/cell contact (Borchers et al, 1997). Thus, the expression pattern of these enzymes are at least partly controlled by the particular extracellular environment, even as the enzymes themselves are capable of altering this environment.…”