Heparanase as a molecular target of cancer chemotherapy
Heparanase as a molecular target of cancer chemotherapy
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DOI：
10.1111/j.1349-7006.2004.tb02485.x
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发表时间：
2004-07
期刊：
影响因子：
5.7
通讯作者：
S. Simizu;K. Ishida;H. Osada
中科院分区：
文献类型：
--
作者：
S. Simizu;K. Ishida;H. Osada
癌细胞需要降解细胞外基质（ECM）的能力，才能转化为侵袭性和转移性癌细胞。许多蛋白酶和糖苷酶在ECM成分的溶解过程中是必不可少的。一种内切β - D -葡萄糖醛酸酶，即肝素酶，能够特异性地降解一种ECM成分，硫酸肝素，这种活性与肿瘤细胞的转移潜力有关。由于肝素酶mRNA在许多人类肿瘤（如肝癌、头颈部肿瘤和食管癌）中过度表达，因此调节肝素酶活性的机制应得到澄清；考虑到肝素酶在癌症中的可能作用，肝素酶抑制剂的发展似乎是有利的。本文将重点介绍近年来在肝素酶的表征、肝素酶mRNA表达转录调控的阐明以及肝素酶抑制剂的发展方面的研究成果。
Cancer cells require the ability to degrade the extracellular matrix (ECM) in order to turn into invasive and metastatic cancer cells. Many proteases and glycosidases are essential in the process of dissolving the components of the ECM. An endo‐β‐D‐glucuronidase, heparanase, is capable of specifically degrading one of the ECM components, heparan sulfate, and this activity is associated with the metastatic potential of tumor cells. Since heparanase mRNA is overexpressed in many human tumors (e.g., hepatomas, head and neck tumors, and esophageal carcinomas), the mechanisms regulating the activity of heparanase should be clarified; considering the possible role of heparanase in cancer, the development of heparanase inhibitors would appear to be advantageous. This review will focus on recent findings that have contributed to the characterization of heparanase and to the elucidation of the transcriptional regulation of heparanase mRNA expression, as well as the development of heparanase inhibitors.