Membrane-bound
peptidases play a key role in the control of growth, differentiation, and signal transduction of many cellular systems by degrading bioactive
peptides. Thus, abnormal changes in their expression pattern and catalytic function result in altered
peptide activation, which contributes to neoplastic transformation or progression. In this review, we describe our recent findings along with work from other groups on the expression and
biological functions of membrane-bound
peptidases in
cancer, focusing on the regulatory roles of three
peptidases,
aminopeptidase A (APA),
neutral endopeptidase (NEP) and
placental leucine aminopeptidase (P-LAP), in the progression of gynecologic
malignancies. APA, NEP and P-LAP are differentially expressed and localized in various gynecologic
malignancies including
cervical cancer,
endometrial cancer,
ovarian cancer and
choriocarcinoma in a
tumor-type specific pattern. The expression levels are up- or down-regulated depending on histological grade or
disease progression. These
peptidases play regulatory roles in
tumor cell proliferation, invasion or angiogenesis via degradation/inactivation of target
peptides such as
angiotensin II,
endothelin-1 and
oxytocin, which act on
cancer cells as stimulatory or inhibitory factors. Thus, membrane-bound
peptidases may become not only a new diagnostic/prognostic marker, but also a novel molecular target for the treatment of gynecologic
malignancies.