title: Extracellular heat shock protein 90: a role for a molecular chaperone in cell motility and cancer metastasis.
abstract: Heat shock protein 90 (Hsp90) is a molecular chaperone whose association is required for the stability and function of multiple mutated, chimeric and over-expressed signaling proteins that promote the growth and/or survival of cancer cells. Hsp90 client proteins include mutated p53, Bcr-Abl, Raf-1, Akt, HER2/Neu (ErbB2) and HIF-1alpha. Hsp90 inhibitors, by interacting specifically with a single molecular target, cause the destabilization and eventual degradation of Hsp90 client proteins, and the first-in-class Hsp90 inhibitor, 17-allylamino-17 demethoxygeldanamycin (17AAG), is currently in phase II clinical trials. A fraction of Hsp90 has been identified at the cell surface and its presence has recently been shown to correlate with melanoma progression. Inhibition of cell-surface Hsp90 with antibodies or cell-impermeable Hsp90 inhibitors blocks cell motility and invasion in vitro and cancer metastasis in vivo. Thus, cell-surface Hsp90 may play a unique role in tumor metastasis, distinct from but perhaps overlapping with its intracellular function. In addition, because cell-surface Hsp90 may be the point of contact between some viruses and host cells, this pool of the chaperone may play a distinct role in initiation of infectious disease.
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, 9000 Rockville Pike, Building 10/CRC, 1-5940, Bethesda, MD 20892, USA.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Len
authors.initials: L
authors.lastname: Neckers
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002465:Cell Movement; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones