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| Content Provider | PubMed Central |
|---|---|
| Author | Banerjee, Aditi Lang, Jing-yu Hung, Mien-chie Sengupta, Krishanu Banerjee, Sushanta K. Baksi, Krishna Banerjee, Dipak K. |
| Copyright Year | 2011 |
| Abstract | Up-regulation of the dolichol pathway, a “hallmark” of asparagine-linked protein glycosylation, enhances angiogenesis in vitro. The dynamic relationship between these two processes is now evaluated with tunicamycin. Capillary endothelial cells treated with tunicamycin were growth inhibited and could not be reversed with exogenous VEGF165. Inhibition of angiogenesis is supported by down-regulation of (i) phosphorylated VEGFR1 and VEGFR2 receptors; (ii) VEGF165-specific phosphotyrosine kinase activity; and (iii) MatrigelTM invasion and chemotaxis. In vivo, tunicamycin prevented the vessel development in MatrigelTM implants in athymic Balb/c (nu/nu) mice. Immunohistochemical analysis of CD34 (p < 0.001) and CD144 (p < 0.001) exhibited reduced vascularization. A 3.8-fold increased expression of TSP-1, an endogenous angiogenesis inhibitor in MatrigelTM implants correlated with that in tunicamycin (32 h)-treated capillary endothelial cells. Intravenous injection of tunicamycin (0.5 mg/kg to 1.0 mg/kg) per week slowed down a double negative (MDA-MB-435) grade III breast adenocarcinoma growth by ∼50–60% in 3 weeks. Histopathological analysis of the paraffin sections indicated significant reduction in vessel size, the microvascular density and tumor mitotic index. Ki-67 and VEGF expression in tumor tissue were also reduced. A significant reduction of N-glycan expression in tumor microvessel was also observed. High expression of GRP-78 in CD144-positive cells supported unfolded protein response-mediated ER stress in tumor microvasculature. ∼65% reduction of a triple negative (MDA-MB-231) breast tumor xenograft in 1 week with tunicamycin (0.25 mg/kg) given orally and the absence of systemic and/or organ failure strongly supported tunicamycin's potential for a powerful glycotherapeutic treatment of breast cancer in the clinic. |
| Related Links | http://dx.doi.org/10.1074/jbc.m110.169771 |
| Ending Page | 29138 |
| Page Count | 12 |
| Starting Page | 29127 |
| File Format | |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | The Journal of Biological Chemistry |
| Issue Number | 33 |
| Volume Number | 286 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2011-08-19 |
| Access Restriction | Open |
| Rights Holder | American Society for Biochemistry and Molecular Biology |
| Subject Keyword | Cell Biology Biochemistry Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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