Targeted disruption of the tissue inhibitor of metalloproteinases gene increases the invasive behavior of primitive mesenchymal cells derived from embryonic stem cells in vitro.

摘要: The metalloproteinase family of proteolytic enzymes can degrade extracellular matrix and facilitate invasive migration. This class is specifically inhibited by the tissue inhibitor metalloproteinases (TIMP-1). Using homologous recombination, we have disrupted gene encoding TIMP-1 in pluripotent embryonic stem cells. Because X linked hemizygous cells, been able to study effect this mutation culture. a basement membrane invasion assay, found that mutant differentiated low concentrations serum with retinoic acid, were more than their normal cell counterparts, was reversed adding exogenous protein. population had characteristics an early primitive mesenchymal including expression vimentin transient period invasiveness from 4-8 d after initiation differentiation. Therefore, activity be rate limiting for invasion.