Pathobiology of the C-cells.

This brief review of the pathobiology of C-cells has stressed cellular and molecular aspects of MTC development. In the genetic forms of MTC, an alteration in one or more genes on chromosome 10, through an as yet unknown series of events, results in initial hyperproliferation of C-cells. Subsequent genetic steps, possibly at other chromosome loci, presumably result in selected clonal transformation of the hyperproliferative C-cells at risk for tumor development. Some of these same molecular events are probably operative in the development of sporadic MTC as well. Once MTC has developed, it has the potential to undergo tumor progression events which result in loss of C-cell differentiation. Studies in a culture model of these events have revealed that activation of signal transduction pathways, similar to those active in differentiation of other neural crest-derived cells, can restore differentiation features of normal C-cells to MTC. Continued identification of the molecular factors mediating this restoration should teach us much about the relationships between general neural crest differentiation and that of normal C-cells. It will also reveal much about the pathobiology of C-cells contributing to each step of MTC development.