92-kD type IV collagenase mediates invasion of human cytotrophoblasts.

TLDR

During early pregnancy, human cytotrophoblasts invade the uterine wall, a process regulated by transient tumor‑like behavior and mediated by metalloproteinases and urokinase‑type plasminogen activator. Inhibition of the 92‑kD type IV collagenase, but not the plasminogen activator system, completely blocks cytotrophoblast invasion, demonstrating its essential role.

Abstract

The specialized interaction between embryonic and maternal tissues is unique to mammalian development. This interaction begins with invasion of the uterus by the first differentiated embryonic cells, the trophoblasts, and culminates in formation of the placenta. The transient tumor-like behavior of cytotrophoblasts, which peaks early in pregnancy, is developmentally regulated. Likewise, in culture only early-gestation human cytotrophoblasts invade a basement membrane-like substrate. These invasive cells synthesize both metalloproteinases and urokinase-type plasminogen activator. Metalloproteinase inhibitors and a function-perturbing antibody specific for the 92-kD type IV collagen-degrading metalloproteinase completely inhibited cytotrophoblast invasion, whereas inhibitors of the plasminogen activator system had only a partial (20-40%) inhibitory effect. We conclude that the 92-kD type IV collagenase is critical for cytotrophoblast invasion.