Structural Requirements of Heparan Sulfate for the Binding to the Tumor-derived Adhesion Factor/Angiomodulin That Induces Cord-like Structures to ECV-304 Human Carcinoma Cells

A High Endothelial Venule Secretory Protein, Mac25/Angiomodulin, Interacts with Multiple High Endothelial Venule-Associated Molecules Including Chemokines

“…As shown in Fig. 1B, mac25/AGM bound strongly to HS and heparin as previously reported (12), moderately to chondroitin sulfate (CS)-E, and weakly to CS-B, CS-D, keratan sulfate, and hyaluronic acid, and failed to interact significantly with CS-A or CS-C. Because HS and various CSs are expressed in the form of proteoglycans in the vascular structure (35), these results also indicate that mac25/AGM interacts with selected members of blood vessel-associated molecules, including HS and certain CSs.…”

“…This apparent discrepancy may be partly due to the fact that mouse mac25/AGM and collagens of the mouse and human origins were used in the present study, whereas human mac25/AGM and bovine collagens were used in the previous studies (10,11). Among the GAGs examined, mac25/AGM showed robust binding to heparin and HS, as reported by others (12), and modest binding to CS-E (Fig. 1B).…”

“…Mac25/AGM is a secreted protein of ϳ30 kDa that is identical with previously reported molecules, including insulin-like growth factor binding protein related protein-1 (IGFBP-rP1) (7-9), tumorderived adhesion factor (10), which was later renamed AGM (11,12), and prostacyclin-stimulating factor (13). Mac25/AGM contains two major domains (9), which include an amino-terminal cysteine-rich domain containing the IGFBP motif that is conserved among IGFBPs and a C-terminal Ig-like domain.…”

“…It has been reported that mac25/AGM increases PGI 2 production in retinal endothelial cells, resulting in an increased retinal blood flow in vivo (14). In addition, mac25/AGM binds to heparan sulfate (HS) glycosaminoglycans (GAGs) (11,12) and has been implicated in angiogenesis (10,11).…”

Glioblastoma-secreted factors induce IGFBP7 and angiogenesis by modulating Smad-2-dependent TGF-β signaling

“…In contrast to the tumor suppressor role of IGFBP7 in cancer cells, IGFBP7 is highly upregulated in vessels of several tumors, including GBM (Akaogi et al, 1996;Pen et al, 2007), and interacts in vitro with various extracellular matrix (ECM) proteins to stimulate adhesion and migration/invasion of vascular endothelial cells on plastic substrates (Sato et al, 1999;Kishibe et al, 2000); hence, the original name 'angiomodulin' (Akaogi et al, 1996). Although literature evidence suggests that IGFBP7 might exhibit angiogenesis-modulating properties (Akaogi et al, 1996;van Beijnum et al, 2006), the role of IGFBP7 in tumor angiogenesis remains poorly understood.…”