Details

Autor(en) / Beteiligte

• Moreno, María J
• Ball, Marguerite
• Rukhlova, Marina
• Slinn, Jacqueline
• L'Abbe, Denis
• Iqbal, Umar
• Monette, Robert
• Hagedorn, Martin
• O'Connor-McCourt, Maureen D
• Durocher, Yves
• Stanimirovic, Danica B

Titel

IGFBP-4 Anti-Angiogenic and Anti-Tumorigenic Effects Are Associated with Anti-Cathepsin B Activity1

Ist Teil von

• Neoplasia (New York, N.Y.), 2013-05, Vol.15 (5), p.554-567

Ort / Verlag

Neoplasia Press Inc

Erscheinungsjahr

2013

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Insulin-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.