Las proteasas en la progresión neoplásica / Proteases in cancer progression

La invasión y la metástasis son los eventos más importantes en la progresión del cáncer, en los cuales están implicadas muchas moléculas, entre ellas, las proteasas. Éstas desempeñan un papel importante en etapas tempranas de la carcinogénesis, en la invasión, en fenómenos asociados como la angiogénesis y en la metástasis, principalmente por su capacidad para degradar componentes de la matriz extracelular, aunque sus sustratos son de naturaleza diversa: citocinas, quimiocinas, factores de crecimiento (b- FGF, HGF, VEGF) y de muerte celular, cistatina-C, galectina, procolágena y otras proteasas, que pueden favorecer o inhibir la progresión neoplásica. Las proteasas son también moléculas de señalización que modulan a otras moléculas; forman cascadas, circuitos e incluso redes, que en conjunto determinan parte del potencial maligno. Se sabe que tanto la célula tumoral como las del estroma secretan diversos factores que regulan directa e indirectamente la expresión de proteasas en el microambiente tumoral. Esta revisión proporciona un panorama breve y actualizado sobre la participación de las proteasas en la progresión neoplásica.

Invasion and metastasis are the most important events in cancer progression. In these two phases, several molecules are implicated and have been long associated with several forms of cancer. Proteases play a critical role not only in tumor cell invasion, but also in the earliest stages of carcinogenesis and its associated changes: angiogenesis and metastasis. Aside from their ability to degrade the extracellular matrix, facilitate invasion and metastasis, proteases target a great variety of substrates that favor or inhibit cancer progression: b-FGF, HGF, VEGF, cell death receptors, cistatin-C, galectin, procollagen, and other proteases. Proteases are also signaling molecules that modulate other molecules by underlying pathways in addition to their degradative role. Proteases form interconnected cascades, circuits and networks that bring about the tumor's potential for malignancy. Although, proteases are regulated by diverse molecules, it is known that tumoral and stromal cells secrete several biological molecules, including cytokines and chemokines that directly or indirectly regulate the protease-expression within the tumor's microenvironment. The present review briefly summarizes some of the major aspects associated with the role of proteases in cancer progression.

Inhibin binding sites in bovine pituitary membranes

Membranes derived from bovine pituitary glands free of the neural lobe were used to investigate the presence of binding sites for inhibin, a glycoprotein produced by the ovarian granulosa cells capable of selectively suppressing FSH secretion from the pituitary gland. Optimal concentration of membranes (400 micrograms prot) and 125I-bovine inhibin (2 nM) were incubated in a medium containing 50 mM Tris-HCl pH 7.4, 0.01 M MgCl2 and BSA 0.01 percent in a final assay volume of 200 microliters at 37 degrees C for different time intervals. Non-specific binding was estimated using unlabelled inhibin in excess. The time course of specific 125I-bovine inhibin (2 nM) binding to bovine pituitary membranes is slow with 50 percent binding at approximately 20 min of incubation and reaching equilibrium at 90 min of incubation. The kinetic analysis shows an apparent pseudo first order association rate constant (Kob) equivalent to 4 x 10(-2) min-1. Following equilibrium with the tracer, a large excess of unlabelled inhibin (1.27 microM) was able to displace 84 percent of the specific binding within 120 min of incubation and 50 percent of the binding at approximately 40 min. The analysis under displacing conditions showed an apparent dissociation rate constant (K2) equals to 1.5 x 10(-2) min-1 and an apparent association rate constant (K1) equals to 1.3 x 10(9) M min-1. Thus, the estimation of the apparent kinetic equilibrium dissociation constant (Kd = K2/K2) of the binding of inhibin to bovine pituitary membranes was 1.2 nM. These results show for the first time the existence of bovine inhibin specific binding sites in bovine pituitary, and also that such a binding can take place in the absence of either gonadal and/or hypothalamic influences. They also contribute to the better understanding of the role of non-steroidal hormones such as inhibin, in the regulation of gonadotrophin secretion

Avances en la estructura y función de la membrana basal / Advances in basement membrane structure and function

La zona de membrana basal es una estructura compleja. Está constituída por la membrana plasmática de la célula basal, lámina lúcida, lámina densa y región de anclaje; cada una de ellas posee diversos componentes moleculares. Sus principales funciones biológicas son actuar como soporte y barrera mecánica, permite la fijación dermoepidérmica, regular la filtración y permeabilidad y guiar la regeneración tisular