Emerging roles for hyaluronidase in cancer metastasis and therapy.
Emerging roles for hyaluronidase in cancer metastasis and therapy.
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DOI：
10.1016/b978-0-12-800092-2.00001-0
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发表时间：
2014
影响因子：
--
通讯作者：
Simpson, Melanie A.
中科院分区：
文献类型：
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作者：
McAtee, Caitlin O.;Barycki, Joseph J.;Simpson, Melanie A.
透明质酸酶是一个由五种人类酶组成的家族，在临床和功能研究中，它们在许多实体肿瘤类型的进展中都有不同的作用。过去五年的进展已经澄清了许多明显的矛盾，(1)通过证明特定的透明质酸酶具有替代透明质酸（HA）的底物或不表现出任何酶活性，(2)高分子量的透明质酸聚合物引发的信号效应与透明质酸酶消化的HA低聚物相反，(3)实际上是透明质酸合成酶与透明质酸酶联合过表达才具有致瘤潜力。本文回顾了支持这些结论的文献，并讨论了透明质酸酶影响侵袭性肿瘤细胞过程的新机制。此外，对透明质酸酶进行了详细的结构和功能比较，并对底物选择性和治疗靶向潜力进行了深入研究。最后，综述了透明质酸酶靶向肿瘤成像和肿瘤治疗的技术进展。
Hyaluronidases are a family of five human enzymes that have been differentially implicated in the progression of many solid tumor types, both clinically and in functional studies. Advances in the past five years have clarified many apparent contradictions, (1) by demonstrating that specific hyaluronidases have alternative substrates to hyaluronan (HA) or do not exhibit any enzymatic activity, (2) that high molecular weight HA polymers elicit signaling effects that are opposite those of the hyaluronidase-digested HA oligomers, and (3) that it is actually the combined overexpression of HA synthesizing enzymes with hyaluronidases that confers tumorigenic potential. This review examines the literature supporting these conclusions and discusses novel mechanisms by which hyaluronidases impact invasive tumor cell processes. In addition, a detailed structural and functional comparison of the hyaluronidases is presented with insights into substrate selectivity and potential for therapeutic targeting. Finally, technological advances in targeting hyaluronidase for tumor imaging and cancer therapy are summarized.