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Cell Journal، جلد ۱۳، شماره Supplement، صفحات ۰-۰
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عنوان انگلیسی I-25: Targeting Tumor Angiogenesis, Lymphangiogenesis, and Metastasis
چکیده انگلیسی مقاله Angiogenesis plays a fundamental role in tumor growth and metastasis. Endostatin is a potent endogenous angiogenesis inhibitor. We have indentified nucleolin as a novel endostatin receptor. Upon some postmodification, nucleolin translocates to the cell surface by the induction of VEGF and extracellular matrix in tumor blood vessels. Endostatin binds to nucleolin, undergoes internalization by both caveolae and clathrin pathways, and nuclear translocation, further inhibits endothelial cell migration and induces apoptosis via VDAC1. The effect of endostatin on lymphangiogenesis and lymph node metastasis has also been discovered recently. Metastasis is a very complicated process, and consists of a series of steps including vascular remodeling, premetastatic niche formation, and tumor cell invasion. We have found that stromal-derived factor-1 regulates pericyte recruitment and local vascular remodeling in platelet-derived growth factor-BB overexpressing tumors. Moreover, we have discovered that angiopoietin 2, matrix metalloproteinase 3, and 10, secreted by primary tumors, can lead to the increased permeability of pulmonary vasculatures and prepare niche to facilitate distant metastasis. Besides the effect on the local and distant vasculatures, tumor cells themselves can also promote their invasive potential via certain mechanisms. Recently, we have found that heat shock protein 90α (Hsp90α) can be secreted by tumor cells, and extracellular Hsp90α can promote not only tumor angiogenesis but also tumor invasion and metastasis via stabilizing matrix metalloproteinase 2. These findings provide new targets for the cancer therapeutics as well as diagnosis/prognosis biomarkers. Latest clinical trials with long lasting endostatin, guided by its receptor nucleolin and monitored in part by Hsp90α, will also be presented.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/1507
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