Recent studies suggest that
aspartic proteinase Cathepsin D may be implicated in the process of
tumor invasion and
metastasis. In fact several in vitro observations showed that this
proteinase may facilitate the spread of neoplastic cells through different mechanisms related to its proteolytic activity, by acting at different levels of the metastatic cascade.
Cathepsin D may promote
tumor cell proliferation by acting as an autocrine
mitogen through the activation of latent forms of
growth factors or by interacting with
growth factor receptors. The
enzyme was also shown to be able to degrade in vitro extracellular matrix and to activate latent precursors forms of other
proteinases involved in the invasive steps of the metastatic process. Although unequivocal proof of its active role in promoting these processes also in vivo has not been obtained so far, recent clinical observations which showed a positive correlation between levels of expression of
Cathepsin D activity and malignant progression of some human
neoplasms further support this hypothesis. These findings warrant extensive experimental and clinical studies to better assess the pathophysiological role of this
acid proteinase in the spread of neoplastic diseases and suggest new and more selective therapeutic approaches to the treatment of human
neoplasms.