Aspectos biomoleculares del carcinoma basocelular y su relación con la metástasis / Biomolecular aspects of basal cell carcinoma and its relation with metastasis

El carcinoma basocelular es una neoplasia cutánea de crecimiento lento. Rara vez produce metástasis, siendo un modelo ideal para analizar los factores que condicionan la misma. Se han identificado numerosos factores de riesgo: radiación ultravioleta, la cual lesiona directamente al ADN induciendo una inmunodepresión selectiva, algunas cepas del virus papiloma humano y trastornos autosómicos recesivos, donde se identificaron mutaciones del gen supresor del crecimiento tumoral. Actualmente, numerosas líneas de investigación están abocadas al estudio de la baja incidencia de metástasis de éste tumor. En éste carcinoma no existe una disminución en las caderinas epiteliales, las cuales intervienen en la adherencia celular. Asimismo, existe disminución de los receptores de laminina y fibronectina. En la matriz extracelular no se ha observado un aumento de enzimas proteolíticas que la degraden. La inmunovigilancia tumoral está muy activada por medio de un aumento de linfocitos T citolíticos y la producción de interferón gamma. Concluimos que no sólo los queratinocitos neoplásicos intervienen en la metástasis, sino que la matriz extracelular juega un rol preponderante en la escasa incidencia de diseminación de éste tumor, por lo que un estudio exhaustivo de la misma permitiría ser aplicado a otras neoplasias y otorgar una mayor sobrevida

Interaçäo da proteína prion celular com laminina e STI-1 e suas possíveis implicações biológicas / Cellular prion protein interaction with laminin and STI-1 and its possible biological implications

A conversäo da proteína príon celular (PrPc) em sua isoforma anormal PrPsc está associada a uma série de doenças neurodegenerativas, genericamente designadas por doenças priônicas. Embora a literatura tenha enfatizado o estudo do PrPsc e o mecanismo de propagaçäo das doenças de príon, pouco tem sido feito para o entendimento do papel fisiológico do PrPc. Em 1997 nosso grupo descreveu um receptor/ligante para o PrPc utilizando o princípio da hidropaticidade complementar. Neste trabalho isolamos e identificamos este ligante de PrPc como sendo a STI-1 (Stress Inducible Protein-1). In vitro, a STI-1 interage com o PrPc de maneira específica, saturável e com alta afinidade (Kd=8x10-8M)...

Laminin/VLA-6 interactions and T cell function

A growing number of investigators consider extracellular matrix (ECM) proteins to be determinant factors in lymphocyte positioning and activation. One major ECM component is laminin, which is constitutively expressed in the thymus as well as in thymus-dependent areas of peripheral lymphoid organs. In the thymus, laminin is produced by epithelial and dendritic cells, and appears to mediate interactions with thymocytes through specific laminin receptors, in particular the integrin VLA-6. This receptor is also expressed by peripheral T cells, and is apparently involved in effector T cell migration and activation. We showed that CD4+ T lymphocytes from chronic chagasic mice exhibited an increase in the absolute and relative number of cells with high VLA-6 expression. Additionally, it is likely that VLA-6/laminin interactions are required for the development of the CD4+ T cell-dependent anti-myocardial autoreactive process that occurs in these animals. Lastly, laminin can bind to some cytokines, a fact that may represent an additional mechanism by which this extracellular matrix component modulates the behavior of T lymphocytes. Taken together, the present data strongly indicate that interactions involving laminin and VLA-6 are functionally linked to relevant events in T cell physiology, comprising entrance of pro-thymocytes into the thymus, intrathymic T cell migration and differentiation, as well as the functioning of mature T lymphocytes, including effector cells.

Adhesion to laminin is down-regulated upon retinoic acid-induced F9 cell differentiation: a role for alpha6/beta1 integrin

F9 mouse teratocarcinoma cells have a high capacity to adhere to laminin and we identified alpha6/beta1 integrin as the principal laminin-binding protein present in these cells. F9 cells differentiated into parietal endoderm when monolayer cultures were treated with retinoic acid and dibutyryl cyclic AMP. In this process a decreased adherence to laminin was observed due to a lower expression of alpha6/beta1 integrin on the cell surface