Secreted heat shock protein-90 (Hsp90) in wound healing and cancer.
Secreted heat shock protein-90 (Hsp90) in wound healing and cancer.
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DOI：
10.1016/j.bbamcr.2011.09.009
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Tsen F
中科院分区：
文献类型：
--
作者：
Li W;Sahu D;Tsen F
细胞外Hsp 90蛋白，包括“膜结合”，“释放”和“分泌”，首次报道是在二十多年前。只有过去七年的研究才开始揭示Hsp 90何时、如何以及为什么被正常细胞和肿瘤细胞输出的图景。正常细胞响应组织损伤而分泌Hsp 90。肿瘤细胞已经设法组成性地分泌Hsp 90用于组织侵袭。在任何一种情况下，细胞外Hsp 90的充足供应都可以通过其在细胞内异常丰富的储存来保证。分泌的Hsp 90 α的一个充分表征的功能是促进细胞运动，这是伤口愈合和癌症的关键事件。已报道的细胞外Hsp 90 α的靶点包括MMP 2、LRP-1、酪氨酸激酶受体等。分泌的Hsp 90 α的促运动活性存在于连接区和中间结构域之间的边界处的片段内。通过LRP-1抑制其分泌、中和其细胞外作用或中断其信号传导在体外和体内阻断伤口愈合和肿瘤侵袭。在正常组织中，局部应用F-5促进急性和糖尿病伤口愈合远比美国FDA批准的常规生长因子疗法更有效。在癌症中，选择性靶向癌细胞分泌的Hsp 90的F-5区域的药物可能比靶向细胞内Hsp 90的ATP酶的药物更有效且毒性更小。
Extracellular Hsp90 proteins, including “membrane-bound”, “released” and “secreted”, were first reported more than two decades ago. Only studies of the past seven years have begun to reveal a picture for when, how and why Hsp90 get exported by both normal and tumor cells. Normal cells secrete Hsp90 in response to tissue injury. Tumor cells have managed to constitutively secrete Hsp90 for tissue invasion. In either case, sufficient supply of the extracellular Hsp90 can be guaranteed by its unusually abundant storage inside the cells. A well-characterized function of secreted Hsp90α is to promote cell motility, a crucial event for both wound healing and cancer. The reported targets for extracellular Hsp90α include MMP2, LRP-1, tyrosine kinase receptors and possibly more. The pro-motility activity of secreted Hsp90α resides within a fragment at the boundary between linker region and middle domain. Inhibition of its secretion, neutralization of its extracellular action or interruption of its signaling through LRP-1 block wound healing and tumor invasion in vitro and in vivo. In normal tissue, topical application of F-5 promotes acute and diabetic wound healing far more effectively than US FDA-approved conventional growth factor therapy in mice. In cancer, drugs that selectively target the F-5 region of secreted Hsp90 by cancer cells may be more effective and less toxic than those that target the ATPase of the intracellular Hsp90.
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影响因子：
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