Cathepsin D in cancer metastasis: A protease and a ligand

Cathepsin D (cath-D) overexpression in breast cancer cells is associated wi th increased risk of metastasis in patients according to several clinical s tudies. No alterations of pro-cath-D structure or activation have been demo nstrated in cancer cells. However, overexpression and dysrouting of pro-cat h-D in illegitimate compartments could have consequences on tumor progressi on. Transfection of a human cDNA cath-D expression vector increases the met astatic potential of 3Y1-Ad12 embryonic rat tumorigenic cells when intraven ously injected into nude mice. The mechanism by which cath-D increases the incidence of clinical metastasis seems to involve increased cell growth and decreased contact inhibition rather than escape of cancer cells through th e basement membrane. Different mechanisms are discussed by which cath-D cou ld act as a protease following its activation or as a ligand of different m embrane receptors at a more neutral pH.