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Heparanase-enhanced shedding of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis
| Content Provider | Scilit |
|---|---|
| Author | Purushothaman, Anurag Uyama, Toru Kobayashi, Fumi Yamada, Shuhei Sugahara, Kazuyuki Rapraeger, Alan C. Sanderson, Ralph D. |
| Copyright Year | 2010 |
| Description | Heparanase enhances shedding of syndecan-1 (CD138), and high levels of heparanase and shed syndecan-1 in the tumor microenvironment are associated with elevated angiogenesis and poor prognosis in myeloma and other cancers. To explore how the heparanase/syndecan-1 axis regulates angiogenesis, we used myeloma cells expressing either high or low levels of heparanase and examined their impact on endothelial cell invasion and angiogenesis. Medium conditioned by heparanase-high cells significantly stimulated endothelial invasion in vitro compared with medium from heparanase-low cells. The stimulatory activity was traced to elevated levels of vascular endothelial growth factor (VEGF) and syndecan-1 in the medium. We discovered that the heparan sulfate chains of syndecan-1 captured VEGF and also attached the syndecan-1/VEGF complex to the extracellular matrix where it then stimulated endothelial invasion. In addition to its heparan sulfate chains, the core protein of syndecan-1 was also required because endothelial invasion was blocked by addition of synstatin, a peptide mimic of the integrin activating region present on the syndecan-1 core protein. These results reveal a novel mechanistic pathway driven by heparanase expression in myeloma cells whereby elevated levels of VEGF and shed syndecan-1 form matrix-anchored complexes that together activate integrin and VEGF receptors on adjacent endothelial cells thereby stimulating tumor angiogenesis. |
| Related Links | http://www.bloodjournal.org/content/bloodjournal/115/12/2449.full.pdf |
| Ending Page | 2457 |
| Page Count | 9 |
| Starting Page | 2449 |
| DOI | 10.1182/blood-2009-07-234757 |
| Journal | Blood |
| Issue Number | 12 |
| Volume Number | 115 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2010-03-25 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Syndecan Heparanase Angiogenesis Endothelial Invasion Medium Protein Myeloma Cells Stimulated Journal: Blood (Vol- 121, Issue- 12) |
| Content Type | Text |
| Resource Type | Article |
