Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells

Abstract

Cathepsin G is a serine protease secreted by activated neutrophils that play a role in the inflammatory response. Because neutrophils are known to be invading leukocytes in various tumors, their products may influence the characteristics of tumor cells such as the growth state, motility, and the adhesiveness between cells or the extracellular matrix. Here, we demonstrate that cathepsin G induces cell-cell adhesion of MCF-7 human breast cancer cells resulting from the contact inhibition of cell movement on fibronectin but not on type IV collagen. Cathepsin G subsequently induced cell condensation, a very compact cell colony, resulting due to the increased strength of E-cadherin-mediated cell-cell adhesion. Cathepsin G action is protease activity-dependent and was inhibited by the presence of serine protease inhibitors. Cathepsin G promotes E-cadherin/catenin complex formation and Rap1 activation in MCF-7 cells, which reportedly regulates E-cadherin-based cell-cell junctions. Cathepsin G also promotes E-cadherin/protein kinase D1 (PKD1) complex formation, and Go6976, the selective PKD1 inhibitor, suppressed the cathepsin G-induced cell condensation. Our findings provide the first evidence that cathepsin G regulates E-cadherin function, suggesting that cathepsin G has a novel modulatory role against tumor cell-cell adhesion.

Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

“…Here, interstitial fluids extracted from the animals were incubated with synthesized C3f peptides (His 6 -C3f_S 1304 -R 1320 -His 6 ), as the substrate of CPN, with the cleavage sites predicted by bioinformatics tools (e.g. PROSPER (14), http://lightning.med.monash.edu/PROSPER/webserver.html), and marked in Fig. 2A.…”

“…We speculate that a peptidase other than CPN may be more active in either tissue or blood as the tumor matures, leading to a decline in peptides cleaved by CPN. Based on predictions using the program PROSPER (14), we selected cathepsin G as a peptidase that could be responsible for cleaving C3f fragments at the site of “LW”. Other studies have suggested an important role for cathepsin G in tumor progression, especially in metastasis (39).…”

“…Indeed, several studies have presented comprehensive qualitative and quantitative profiling of circulating peptides, demonstrating their enormous potential use as a rapid, cost-effective, and accurate platform for cancer diagnosis and therapeutic evaluation, even despite the complexity cancer pathophysiology landscape (9–13). However, only a few of them have shown a direct correlation between the presence (and/or quantity) of these circulating peptides, the proteases/peptidases that generate them, or the roles these play in cancer progression (12, 14–16). …”

Antibacterial Proteins and Peptides in Nurse Shark (<em>Ginglymostoma Cirratum</em>) Peripheral Blood Leukocytes

“…There are several proteins that are associated with the non-oxidative response in mammalian phagocytic cells that are antimicrobial in nature, one of which is cathepsin G, a serine protease that is found in the azurophilic granules of neutrophils, and some monocytes (Odeberg et al 1975;Senior et al 1982;Spitznagel 1990;Kudo et al 2009). …”

Design and fabrication of engineered platforms to control multiple cue directed cell migration

“…When cell--cell adhesion is significant and in the absence of proliferation, the assembly of clusters can result either from random migration [8, 24--27], paracrine-mediated directed migration [28,29] or mechanically--induced cell compaction [23]. All three induce cell--cell contact and cluster formation when cells collide [30]. In the presence of proliferation, the continual division of well--attached daughter cells can also act to enhance clustering [31].…”