Chemical Tumor Biology of Heparan Sulfate Proteoglycans.
Chemical Tumor Biology of Heparan Sulfate Proteoglycans.
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DOI：
10.2174/187231310790226206
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发表时间：
2010-01-01
影响因子：
--
通讯作者：
Kuberan B
中科院分区：
文献类型：
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作者：
Raman K;Kuberan B
硫酸乙酰肝素蛋白聚糖 (HSPG) 在肿瘤进展的每一步中都发挥着至关重要的作用，使癌细胞能够增殖、逃避免疫反应、侵入邻近组织并转移到远离原发部位的远端部位。包括乳腺癌、肺癌、脑癌、胰腺癌、皮肤癌和结直肠癌在内的多种癌症表现出多种关键 HS 生物合成酶（如 3-O 磺基转移酶和 6-O 磺基转移酶）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 HS 精细结构有助于癌细胞分解 ECM 进行扩散，错误调节信号通路以促进其增殖，促进血管生成以接收营养，并保护自身免受自然杀伤细胞的侵害。本综述重点关注几种癌症中 HS 生物合成和分解代谢酶表达的变化、由此引起的 HS 精细结构的变化，以及这些肿瘤特异性 HS 特征对促进侵袭、增殖和转移的影响。通过新颖的化学生物学方法调节 HS 链失调的生物合成和分解代谢途径，可以延缓肿瘤进展。
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.