tailieunhanh - Báo cáo khoa học: Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting

The expression of proteoglycans (PGs), essential macromolecules of the tumor microenvironment, is markedly altered during malignant transforma-tion and tumor progression. Synthesis of stromal PGs is affected by factors secreted by cancer cells and the unique tumor-modified extracellular matrix may either facilitate or counteract the growth of solid tumors. | MINIREVIEW Proteoglycans in health and disease novel roles for proteoglycans in malignancy and their pharmacological targeting Achilleas D. Theocharis1 Spyridon S. Skandalis2 George N. Tzanakakis3 and Nikos K. Karamanos1 1 Laboratory of Biochemistry Department of Chemistry University of Patras Greece 2 Ludwig Institute for Cancer Research Ltd Uppsala Sweden 3 Department of Histology University of Crete Heraklion Greece Keywords cancer decorin glypicans lumican molecular targeting perlecan proteoglycans serglycin syndecans versican Correspondence N. Karamanos Laboratory of Biochemistry Department of Chemistry University of Patras 26100 Patras Greece Fax 30 2610 997153 Tel 30 2610 997915 E-mail Received 3 May 2010 revised 15 July 2010 accepted 29 July 2010 doi The expression of proteoglycans PGs essential macromolecules of the tumor microenvironment is markedly altered during malignant transformation and tumor progression. Synthesis of stromal PGs is affected by factors secreted by cancer cells and the unique tumor-modified extracellular matrix may either facilitate or counteract the growth of solid tumors. The emerging theme is that this dual activity has intrinsic tissue specificity. Matrix-accumulated PGs such as versican perlecan and small leucine-rich PGs affect cancer cell signaling growth and survival cell adhesion migration and angiogenesis. Furthermore expression of cell-surface-associated PGs such as syndecans and glypicans is also modulated in both tumor and stromal cells. Cell-surface-associated PGs bind various factors that are involved in cell signaling thereby affecting cell proliferation adhesion and motility. An important mechanism of action is offered by a proteolytic processing of cell-surface PGs known as ectodomain shedding of syndecans this facilitates cancer and endothelial cell motility protects matrix proteases and provides a chemotactic gradient of mitogens. However syndecans on .