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Author Vlodavsky, Israel ♦ Beckhove, Phillip ♦ Lerner, Immanuel ♦ Pisano, Claudio ♦ Meirovitz, Amichai ♦ Ilan, Neta ♦ Elkin, Michael
Source SpringerLink
Content type Text
Publisher Springer Netherlands
File Format PDF
Copyright Year ©2011
Language English
Subject Domain (in DDC) Technology ♦ Medicine & health
Subject Keyword Extracellular matrix ♦ Tumor microenvironment ♦ Inflammation ♦ Tumor associated macrophages ♦ Heparan sulfate ♦ Heparanase ♦ Metastasis ♦ Colitis ♦ Colon carcinoma ♦ Cell Biology ♦ Immunology ♦ Biomedicine general ♦ Biochemistry ♦ Oncology ♦ Cancer Research
Abstract Heparan sulfate proteoglycans (HSPGs) are primary components at the interface between virtually every eukaryotic cell and its extracellular matrix. HSPGs not only provide a storage depot for heparin-binding molecules in the cell microenvironment, but also decisively regulate their accessibility, function and mode of action. As such, they are intimately involved in modulating cell invasion and signaling loops that are critical for tumor growth, inflammation and kidney function. In a series of studies performed since the cloning of the human heparanase gene, we and others have demonstrated that heparanase, the sole heparan sulfate degrading endoglycosidase, is causally involved in cancer progression, inflammation and diabetic nephropathy and hence is a valid target for drug development. Heparanase is causally involved in inflammation and accelerates colon tumorigenesis associated with inflammatory bowel disease. Notably, heparanase stimulates macrophage activation, while macrophages induce production and activation of latent heparanase contributed by the colon epithelium, together generating a vicious cycle that powers colitis and the associated tumorigenesis. Heparanase also plays a decisive role in the pathogenesis of diabetic nephropathy, degrading heparan sulfate in the glomerular basement membrane and ultimately leading to proteinuria and kidney dysfunction. Notably, clinically relevant doses of ionizing radiation (IR) upregulate heparanase expression and thereby augment the metastatic potential of pancreatic carcinoma. Thus, combining radiotherapy with heparanase inhibition is an effective strategy to prevent tumor resistance and dissemination in IR-treated pancreatic cancer patients. Also, accumulating evidence indicate that peptides derived from human heparanase elicit a potent anti-tumor immune response, suggesting that heparanase represents a promising target antigen for immunotherapeutic approaches against a broad variety of tumours. Oligosaccharide-based compounds that inhibit heparanase enzymatic activity were developed, aiming primarily at halting tumor growth, metastasis and angiogenesis. Some of these compounds are being evaluated in clinical trials, targeting both the tumor and tumor microenvironment.
ISSN 18752292
Age Range 18 to 22 years ♦ above 22 year
Educational Use Research
Education Level UG and PG
Learning Resource Type Article
Publisher Date 2011-08-03
Publisher Institution International Cancer Microenvironment Society
Publisher Place Dordrecht
e-ISSN 18752284
Journal Cancer Microenvironment
Volume Number 5
Issue Number 2
Page Count 18
Starting Page 115
Ending Page 132

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Source: SpringerLink