La hiperplasia epidérmica observada en carcinoma basocelular podría involucrar la migración e invasión colectiva de los queratinocitos: posible papel del receptor CD44 y la tirosina quinasa c-Src en su forma activada

Resumen

Introduccion: La migracion colectiva es un proceso complejo donde grupos de celulas que mantienen sus contactos entre si se mueven juntas como una unidad multicelular a traves de matrices extracelulares, siendo reactivada durante la progresion tumoral. Objetivos: Determinar los eventos celulares relacionados con la migracion colectiva de queratinocitos basales y suprabasales en biopsias de piel de pacientes con carcinoma basocelular superficial, morfeiforme y piel normal. Metodologia: En este estudio se realizo el analisis histologico in vivo de 6 biopsias de pacientes con carcinoma basocelular superficial y 5 biopsias de carcinomas basocelulares morfeiformes que exhibian una epidermis hiperplasica, comparadas con 3 biopsias de piel normal. Se realizo microscopia confocal para analizar la presencia de CD44 y p-c-Src. Resultados: La observacion a mayor aumento de estas biopsias demostro que algunas celulas basales y suprabasales de la epidermis estaban organizadas en grupos multicelulares orientados hacia la dermis papilar y muchas de ellas se mantenian juntas a traves de puentes o uniones intercelulares. La microscopia confocal revelo la presencia de CD44 delineando los margenes y puentes intercelulares de celulas basales y suprabasales que estaban orientadas hacia la dermis papilar, mientras que c-Src activado se localizo en las uniones celula-celula exhibiendo un patron similar al de CD44, encontrandose ademas en las protrusiones membranales donde la presencia de CD44 aparecia interrumpida. Conclusiones: La hiperplasia observada en biopsias examinadas de carcinomas basocelulares podria involucrar la migracion e invasion colectiva de algunos queratinocitos basales y suprabasales hacia la dermis, donde CD44 y p-c-Src posiblemente desempenan un papel importante. Epidermal hyperplasia observed in basocellular cancer could involve migration and collective invasion of keratocytes: possible role of the CD44 receptor and C-Src tyrosine kinase in its activated form Abstract: Background: Collective cell migration is a complex process in which groups of cells that have retained their contacts with each other move together as a unit multicellular through extracellular matrices, and being reactivated during tumor progression. Objective: To determine the cellular events associated with collective migration in basal and suprabasal keratinocytes in skin biopsies from patients with superficial basal cell carcinoma, morphoeic, and normal skin. Methods: In this study the presence of CD44 and p-c-Src was examined by confocal microscopy in 6 biopsies of patients with diagnostic of superficial basal cell carcinoma and 5 with diagnostic of morphoeic basal cell carcinoma biopsies exhibiting a hyperplastic epidermis and compared with 3 normal skin biopsies. Results: Histological analysis of these biopsies showed that basal and suprabasal cells of the epidermis were organized into multicellular groups oriented toward papillary dermis and many of them stuck together through intercellular bridges or junctions. Confocal microscopy revealed the presence of CD44 and delineating margins of basal cell intercellular bridges and suprabasal that were oriented toward the papillary dermis, whereas activated c-Src was localized to cell-cell junctions exhibiting a similar pattern of CD44, and in the membrane protrusions where the presence of CD44 appeared interrupted. Conclusion: The observed hyperplasia of basal cell carcinomas examined biopsies could involve collective migration and invasion of some basal and suprabasal keratinocytes into the dermis, where CD44 and pc-Src possibly play an important role.