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Recombinant semaphorin 6A-1 ectodomain inhibits in vivo growth factor and tumor cell line-induced angiogenesis
| Content Provider | Scilit |
|---|---|
| Author | Dhanabal, Mohanraj Wu, Frank Alvarez, Enrique McQueeney, Kelly D. Jeffers, Mike Dougall, John Mac Boldog, Ferenc L. Hackett, Craig Shenoy, Suresh Khramtsov, Nikolai Weiner, Jami Lichenstein, Henri S. LaRochelle, William J. |
| Copyright Year | 2005 |
| Description | Journal: Cancer Biology & Therapy The Semaphorins are a large family of transmembrane, GPI-anchored and secreted proteins that play an important role in neuronal and endothelial cell guidance. A human gene related to the class VI Semaphorin family, Semaphorin 6A-1 (Sema 6A-1) was identified by homology-based genomic mining. Recent implication of Sema 3 family members in tumor angiogenesis and our expression analysis of Sema 6A-1 suggested that class VI Semaphorin might effect tumor neovascularization. The mRNA expression of Sema 6A-1 was elevated in several renal tumor tissue samples relative to adjacent non-tumor tissue samples from the same patient. Sema 6A-1 transcript was also expressed in the majority of renal clear cell carcinoma (RCC) cell lines and to a lesser extent in endothelial cells. To test the role of Sema 6A-1 in tumor angiogenesis, we engineered, expressed and purified the Sema 6A-1 soluble extracellular domain (Sema-ECD). The purified Sema-ECD was screened in a variety of endothelial cell-based assay both in vitro and in vivo. In vitro, Sema-ECD blocked VEGF-mediated endothelial cell migration. These effects were explained in part by our observation in endothelial cells that Sema-ECD inhibited VEGF-mediated Src, FAK and ERK phosphorylation. In vivo, mouse Matrigel assays demonstrated that the intraperitoneal administration of recombinant Sema-ECD inhibited both bFGF/VEGF and tumor cell line-induced neovascularization. These findings reveal a novel therapeutic utility for Sema 6A-1 (Sema-ECD) as an inhibitor of growth factor as well as tumor-induced angiogenesis. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.4161/cbt.4.6.1733?needAccess=true |
| Ending Page | 668 |
| Page Count | 10 |
| Starting Page | 659 |
| ISSN | 15384047 |
| e-ISSN | 15558576 |
| DOI | 10.4161/cbt.4.6.1733 |
| Journal | Cancer Biology & Therapy |
| Issue Number | 6 |
| Volume Number | 4 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2005-06-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cancer Biology & Therapy Biochemistry and Molecular Biology Tumor Cell Line Cell Line Induced Tumor Angiogenesis Neovascularization Induced Angiogenesis |
| Content Type | Text |
| Subject | Cancer Research Pharmacology Molecular Medicine Oncology |
