Roles of Hsp90 in wound healing and cancer

     Wound healing is an intricate process in which the skin (or another organ-tissue) repairs itself after injury. At present, local growth factors are considered to be the driving force for wound healing and only recombinant human platelet-derived growth factor-BB (PDGF-BB) has been approved by US FDA for topical treatment of diabetic ulcers. However, the use of PDGF-BB in clinical trials has been limited for its modest efficacy, high cost and risk of causing cancer. Thus, novel treatment for wound healing is needed to be explored.

     Hsp90 (heat shock protein 90), as a molecular chaperone, is one of the most abundant proteins expressed in cells. The function of Hsp90 mainly includes assisting in protein folding, cell signaling, and tumor repression. Recently, researchers found that secreted Hsp90α promotes wound closure in mice more strongly than the becaplermin gel[1].
     There are fundamental distinctions between intracellular and extracellular Hsp90, since one acts as a chaperone inside and the other as a pro-motility factor outside. Generally, normal cells do not secrete Hsp90, while many pathological and stress conditions may promote normal cells to secrete Hsp90, such as reactive oxygen species (ROS), heat, hypoxia, gamma-irradiation and tissue injury-released cytokines, such as TGFα. Some studies reported that secretion of Hsp90α would become constitutive in those HIF-1α- overexpressing tumors, since HIF-1α is identified as a key upstream regulator of Hsp90α secretion. Why has eHsp90α shown more effective therapy than the conventional growth factor? The answer is that Hsp90 is a common pro-motility factor for all three types of human skin cells involved in wound healing and thus remains equally effective to promote the cell migration[2]. When wound healing happenes in a solid tumor and will induce the angiogenesis and growth of tumor. In this condition, Hsp90 becomes a clinical target[2].
     In summary, Hsp90 has two important roles: an intracellular chaperone and an extracellular tissue-repairing factor. Its role in tissue repair and cancer invasion has make it a novel therapeutic intervention, and It may be a crucial tool for cancers treatment to develop inhibitors of HSP90.
 

References
[1]. EMBO J. 26 (2007) 1221–1233..
[2]. Biochim. Biophys. Acta (2011), doi:10.1016/j.bbamcr.2011.09.009.

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HSP (HSP90)