Internalization of cystatin C in human cell lines (original) (raw)

Altered protease activity is thought to be important in tumour cell invasion and metastasis, and to have a profound role in angiogenesis. Implicated proteases belong to the serine, metallo-, aspartic and cysteine protease classes. The latter comprises more than 30 protein families [1], including family C1 with mammalian enzymes like cathepsins B and L involved in cancer growth and metastasis . Since the involvement of cathepsin B in cancer metastasis was originally described by Sloane et al. [3], cathepsins, and especially cathepsin B, have been studied thoroughly. The activity of the C1 family of cysteine proteases is balanced by tight-binding inhibitors, the cystatins [4]. The cystatin protein family comprises three major groups of inhibitors: type 1 cystatins, also called stefins, which are intracellular proteins present in most cells (cystatin A and B); type 2 cystatins, which are extracellular inhibitors found in most body fluids (cystatin C, D, E ⁄ M, F, G, H, S, SA and SN); and type 3, which are multidomain proteins, the kininogens. Among the