Abstract 2469: Increased cathepsin B expression in cultured tuberous sclerosis skin tumor cells and patient tumor tissues

Abstract

Abstract Skin hamartomas in tuberous sclerosis complex (TSC) are disfiguring red tumors that contain fibroblast-like cells, vessels, fibrous tissue, and elongated hair follicles. Our recent studies show that TSC skin tumor cells induce angiogenesis and hair follicle neogenesis in a xenograft mouse model. These morphogenic changes are likely caused by altered expression of proteins involved in tissue remodeling. To identify such factors, we carried out 2-D gel analysis of cell extracts of TSC2-null fibroblasts derived from a TSC periungual fibroma (PF) compared to fibroblasts from patient normal-appearing skin (NL). PF cells had greater levels of all three forms of cathepsin B than TSC normal fibroblasts. Cathepsin B, a member of the lysosomal cysteine proteases family that has been implicated in angiogenesis and extracellular matrix remodeling, exists in pro-, single chain and double chain forms, and these were increased in PF cells by 1.6-, 2.3- and 8.3-fold, respectively. Western blot analysis of TSC skin tumor fibroblasts from 5 patients showed dramatically greater levels of active cathepsin B than in paired patient NL fibroblasts. Tumor cells from PFs showed greater intracellular cathepsin B enzyme activity than NL controls. Western blot and ELISA analysis showed that media conditioned by TSC skin tumor cells from 5 different patients contained 4.1- to 36-fold more procathepsin B than media conditioned by NL fibroblasts. Immunohistochemical staining of TSC patient angiofibromas and PFs showed greater numbers of cathepsin B-positive cells than patient normal-appearing skin. These results suggest that TSC skin tumor cells may induce hamartoma morphogenesis through expressing and releasing high level of cathepsin B. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2469. doi:1538-7445.AM2012-2469