期刊
ADVANCED DRUG DELIVERY REVIEWS
卷 97, 期 -, 页码 156-173出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.addr.2015.10.012
关键词
Proteoglycan; Angiogenesis; Autophagy; Collagen type XVIII; Perlecan
资金
- NIH [CA39481, CA47282]
- German Research Council [SFB 815, A5, SFB 1039, B2, SCHA 1082/6-1]
- LOEWE program Ub-Net
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. (C) 2015 Elsevier B.V. All rights reserved.
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