Raman Karthik, Kuberan Balagurunathan
Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
Curr Chem Biol. 2010 Jan 1;4(1):20-31. doi: 10.2174/187231310790226206.
Heparan sulfate proteoglycans (HSPGs) play vital roles in every step of tumor progression allowing cancer cells to proliferate, escape from immune response, invade neighboring tissues, and metastasize to distal sites away from the primary site. Several cancers including breast, lung, brain, pancreatic, skin, and colorectal cancers show aberrant modulation of several key HS biosynthetic enzymes such as 3-O Sulfotransferase and 6-O Sulfotransferase, and also catabolic enzymes such as HSulf-1, HSulf-2 and heparanase. The resulting tumor specific HS fine structures assist cancer cells to breakdown ECM to spread, misregulate signaling pathways to facilitate their proliferation, promote angiogenesis to receive nutrients, and protect themselves against natural killer cells. This review focuses on the changes in the expression of HS biosynthetic and catabolic enzymes in several cancers, the resulting changes in HS fine structures, and the effects of these tumor specific HS signatures on promoting invasion, proliferation, and metastasis. It is possible to retard tumor progression by modulating the deregulated biosynthetic and catabolic pathways of HS chains through novel chemical biology approaches.
硫酸乙酰肝素蛋白聚糖（HSPGs）在肿瘤进展的每一步都发挥着至关重要的作用，使癌细胞得以增殖、逃避免疫反应、侵袭邻近组织并转移至远离原发部位的远处。包括乳腺癌、肺癌、脑癌、胰腺癌、皮肤癌和结直肠癌在内的几种癌症，均表现出几种关键的硫酸乙酰肝素生物合成酶（如3 - O硫酸转移酶和6 - O硫酸转移酶）以及分解代谢酶（如HSulf - 1、HSulf - 2和乙酰肝素酶）的异常调节。由此产生的肿瘤特异性硫酸乙酰肝素精细结构，有助于癌细胞分解细胞外基质以扩散、错误调节信号通路以促进其增殖、促进血管生成以获取营养，并保护自身免受自然杀伤细胞的攻击。本综述重点关注几种癌症中硫酸乙酰肝素生物合成和分解代谢酶表达的变化、硫酸乙酰肝素精细结构的相应变化，以及这些肿瘤特异性硫酸乙酰肝素特征对促进侵袭、增殖和转移的影响。通过新型化学生物学方法调节硫酸乙酰肝素链失调的生物合成和分解代谢途径，有可能延缓肿瘤进展。
