PLASMINOGEN ACTIVATORS IN BREAST-CANCER CELLS

This review summarizes recent experimental and clinical studies on plasminogen activator (PA) expression in breast cancer cells. The two PAs, urokinase-type (u-PA) and tissue-type (t-PA), have quite different biological significance in breast cancer cells. Sufficient evidence indicates that t-PA production is regulated by estrogen via an estrogen receptor system and suggests the potential usefulness of this enzyme as a marker for estrogen action in breast cancer cells. On the other hand, u-PA has been implicated in cancer cell invasion and metastasis formation because this enzyme can degrade components of the extracellular matrices and basement membranes either directly through its enzyme activity or indirectly by activation of other proteinases. High levels of u-PA correlates with both shortened disease-free survival and overall survival in patients with breast cancer indicating that u-PA is a new prognostic marker in human breast cancer. In contrast to u-PA, t-PA is associated with a good prognosis. However, t-PA is involved in bone-only metastasis formation by its effects through the vertebral venous plexus.