IGFBP-4 anti-angiogenic and anti-tumorigenic effects are associated with anti-cathepsin B activity

Download
  1. Get@NRC: IGFBP-4 anti-angiogenic and anti-tumorigenic effects are associated with anti-cathepsin B activity (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1593/neo.13212
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titleNeoplasia (United States)
ISSN1522-8002
Volume15
Issue5
Pages554567; # of pages: 14
Subjectcathepsin B; somatomedin binding protein 1; somatomedin binding protein 4; angiogenesis; animal experiment; animal model; animal tissue; antiangiogenic activity; antineoplastic activity; article; cancer transplantation; cell anchorage; cell growth; cell viability; confocal laser microscopy; controlled study; glioblastoma; human; human cell; male; mouse; nonhuman; priority journal; tissue section; tumor growth
AbstractInsulin-like growth factor-binding protein 4 (IGFBP-4/IBP-4) has potent IGF-independent anti-angiogenic and antitumorigenic effects. In this study, we demonstrated that these activities are located in the IGFBP-4 C-terminal protein fragment (CIBP-4), a region containing a thyroglobulin type 1 (Tg1) domain. Proteins bearing Tg1 domains have been shown to inhibit cathepsins, lysosomal enzymes involved in basement membrane degradation and implicated in tumor invasion and angiogenesis. In our studies, CIBP-4 was shown to internalize and co-localize with lysosomal-like structures in both endothelial cells (ECs) and glioblastoma U87MG cells. CIBP-4 also inhibited both growth factor-induced EC tubulogenesis in Matrigel and the concomitant increases in intracellular cathepsin B (CatB) activity. In vitro assays confirmed CIBP-4 capacity to block recombinant CatB activity. Biodistribution analysis of intravenously injected CIBP-4-Cy5.5 in a glioblastoma tumor xenograft model indicated targeted accumulation of CIBP-4 in tumors. Most importantly, CIBP-4 reduced tumor growth in this animal model by 60%. Pleiotropic anti-angiogenic and anti-tumorigenic activities of CIBP-4 most likely underlie its observed therapeutic potential against glioblastoma. © 2013 Neoplasia Press, Inc.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC)
Peer reviewedYes
NPARC number21270681
Export citationExport as RIS
Report a correctionReport a correction
Record identifier47c8a2b6-dc22-4121-b871-9ed7cdd45733
Record created2014-02-17
Record modified2016-05-09
Bookmark and share
  • Share this page with Facebook (Opens in a new window)
  • Share this page with Twitter (Opens in a new window)
  • Share this page with Google+ (Opens in a new window)
  • Share this page with Delicious (Opens in a new window)