EMBRYOGENESIS, REPAIR AND TUMORIGENESIS AS DEFINED BY A CONSERVED EXTRACELLULAR-MATRIX .1.

Similarities between tissue repair, tumorigenesis, and embryonic devel opment have been proposed for some years, largely on intuitive grounds , but more recently on the basis of experimental findings. It is obvio us that all three processes include cellular proliferation and migrati on, representing mechanisms by which normal or modified morphogenesis is defined, but it is less obvious that the extracellular milieu has a central role in the organization of these processes. In this review w e place these three processes in their appropriate evolutionary contex ts by examining the origins of the extracellular matrix, arising with the first metazoa, and analyzing its critical function in regulating c ellular behavior. Biphasic embryogenesis was the mechanism that allowe d the first complex metazoa to evolve, the defining moment that accoun ts for the Cambrian explosion. All other forms of cellular behavior an d regulation can be seen as adaptations of this crucial, central, them e. Tissue-repair mechanisms bear similarities to events occurring in e mbryogenesis, whereas tumorigenesis may be considered as a ''caricatur e'' of tissue renewal in which the embryogenic process proceeds in the absence of normal regulatory constraints. From this it can be inferre d that repair, tumorigenesis and development involve highly-conserved evolutionarily-ancient processes. In all these processes, the collagen ous extracellular matrix defines tissue architecture, maintains morpho logy and interacts with cells via specific sequences on the various ma trix components.