The role of cellular plasticity in cancer development.

It has traditionally been accepted that, in the process of cellular differentiation, developmental options are progressively restricted until commitment to a specific fate is established and then only terminal differentiation along this lineage is possible. Although this is usually the case in normal physiological development, the latest experimental evidences indicate that the differentiated state of mature cells is not always as stable and durable as it was thought to be. In fact, recently, a hidden plasticity has been revealed in differentiated cells which allows them to deviate to other cell types that might be, functionally, very far away in other developmental pathways. This plasticity has biological significance since it is necessary for normal development to occur, but it also makes possible the emergence of aberrant lineages when interferences with the normal transcriptional and epigenetic mechanisms in charge of maintaining cellular identity do appear. Cancer is one of the possible outcomes of this aberrant reprogramming. The plasticity of the initial cell suffering the first oncogenic alteration plays an essential role in cancer development, since only if this cell possesses enough plasticity a tumoral reprogramming will be possible and a full-blown tumor will develop. Also, plasticity makes it possible for differentiated cells to acquire cancer stem cell properties in the presence of the appropriate oncogenic insults. In this review we discuss the role of cellular plasticity in the normal development of adult tissues and how cellular susceptibility to reprogramming plays an essential part in cancer development.

Differential patterns of filaggrin expression in lamellar ichthyosis.

Lamellar ichthyosis (LI) is a rare genetic and congenital disturbance of keratinization that is phenotypically and genotypically heterogeneous. Filaggrin is one of the major components of the stratum corneum situated in the protein matrix and the cornified envelope. In view of the heterogeneity of LI, this study aimed at exploring filaggrin expression in the skin of patients suffering from the disease. Epidermal filaggrin expression was determined using immunohistochemical techniques and Western blot in 12 patients with LI and the findings were compared with those observed in four normal controls and eight patients with ichthyosis vulgaris. With Western blot, six different patterns of filaggrin expression were detected. The patients with similar clinical manifestations showed a similar pattern, as did members of the same family. Overall, higher filaggrin expression in scales correlated with a better prognosis. In patients receiving retinoids no variations in filaggrin expression during treatment were detected. Our results suggest that LI is heterogeneous as regards filaggrin expression. Filaggrin could therefore be used as a prognostic marker as well as being a marker of the basic defect involved in LI.