title: Secreted heat shock protein-90 (Hsp90) in wound healing and cancer.
abstract: Extracellular Hsp90 proteins, including "membrane-bound", "released" and "secreted", were first reported more than two decades ago. Only studies of the past 7years have begun to reveal a picture for when, how and why Hsp90 gets 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, called 'F-5', 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. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90).
authors: The Department of Dermatology, the University of Southern California, Los Angeles, CA, USA. wli@usc.edu
authors: Wei
authors: W
authors: Li
authors: Divya
authors: D
authors: Sahu
authors: Fred
authors: F
authors: Tsen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism* / Q000503:physiopathology*; D015398:Signal Transduction; D014945:Wound Healing / Q000502:physiology*
chemical_list: D018841:HSP90 Heat-Shock Proteins