Proteolytic cleavage of membrane proteins by membrane type-1 MMP regulates cancer malignant progression.

Strategies to develop cancer therapies using inhibitors that target matrix metalloproteinases (MMPs), particularly membrane type-1 MMP (MT1-MMP), have failed. This is predominantly attributed to the specificity of MMP inhibitors and numerous functions of MMPs; therefore, targeting substrates with such broad specificity can lead to off-target effects. Thus, new drug development for cancer therapeutics should focus on the ability of MT1-MMP to break down substrates, such as functional cell membrane proteins, to regulate the functions of these proteins that promote tumor malignancy. In this review, we discuss the mechanism by which proteolysis of cell surface proteins by MT1-MMP promotes progression of malignant tumor cells. In addition, we discuss the two protein fragments generated by limited cleavage of erythropoietin-producing hepatoma receptor tyrosine kinase A2 (EphA2-NF, -CF), which represent a promising basis for developing new cancer therapies and diagnostic techniques.

Facile Post-Carboxymethylation of Cellulose Nanofiber Surfaces for Enhanced Water Dispersibility.

To improve the water dispersibility of cellulose nanofibers without deteriorating the physical properties, it is necessary to develop methods that can selectively modify fiber surfaces. Herein, the reaction conditions for carboxymethylation of the surface of nanofibrillated bacterial cellulose were optimized using chloroacetic acid as an etherification agent. Carboxymethylation in a high-concentration alkaline solution (>5 wt %) in the presence of isopropanol caused the mercerization and carboxymethylation of not only the nanofiber surface but also the cellulose crystals within the nanofiber, resulting in nanofiber swelling and an increase in fiber width. In contrast, with a dilute alkaline aqueous solution (3 wt %), the nanofiber surface was successfully carboxymethylated without changing the inner structure. Furthermore, the morphology was not affected by the carboxymethylation reaction, and no fiber swelling occurred under these reaction conditions. When the substitution reaction proceeded only on the nanofiber surface, the maximum degree of substitution (i.e., the average number of carboxymethyl groups substituted per anhydroglucose residue in cellulose) was 0.091. After surface modification, the nanofibers became more negatively charged, which improved the dispersibility in water through electrostatic repulsion, resulting in a drastic increase in the transparency of the nanofiber dispersion. This method provides a general approach for the surface modification of cellulose nanofibers to increase water dispersibility.