Endostatin and endorepellin: A common route of action for similar angiostatic cancer avengers

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• 作者：Chiara Poluzzi^a ; Renato V. Iozzo^b ; Liliana Schaefer^a ; ^{Schaefer@med.uni-frankfurt.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PCD ; programmed cell death ; NC1 ; non-collagenous sequence 1 ; VEGFR1/2 ; vascular endothelial growth factor receptor 1/2 ; CAM ; chick chorioallantoic membrane ; MMPs ; matrix metalloproteinases ; GAP ; GTPase-activating protein ; FAK ; focal adhesion kinase ; MAPK ; mitogen-activated protein kinase ; ERK ; extracellular signal-regulated kinase ; HIF-1α ; hypoxia-inducible factor 1-alpha ; VEGFA ; vascular endothelial growth factor A ; VEGF ; vascular endothelial growth factor ; Wnt ; wingless-type MMTV integration s
• 刊名：Advanced Drug Delivery Reviews
• 出版年：2016
• 出版时间：1 February 2016
• 年：2016
• 卷：97
• 期：Complete
• 页码：156-173
• 全文大小：1557 K

文摘

Traditional cancer therapy typically targets the tumor proper. However, newly-formed vasculature exerts a major role in cancer development and progression. Autophagy, as a biological mechanism for clearing damaged proteins and oxidative stress products released in the tumor milieu, could help in tumor resolution by rescuing cells undergoing modifications or inducing autophagic-cell death of tumor blood vessels. Cleaved fragments of extracellular matrix proteoglycans are emerging as key players in the modulation of angiogenesis and endothelial cell autophagy. An essential characteristic of cancer progression is the remodeling of the basement membrane and the release of processed forms of its constituents. Endostatin, generated from collagen XVIII, and endorepellin, the C-terminal segment of the large proteoglycan perlecan, possess a dual activity as modifiers of both angiogenesis and endothelial cell autophagy. Manipulation of these endogenously-processed forms, located in the basement membrane within tumors, could represent new therapeutic approaches for cancer eradication.