Secretion of extracellular hsp90α via exosomes increases cancer cell motility: a role for plasminogen activation

BMC Cancer

Research Article

Jessica McCready¹  Jessica D Sims¹  Daniel G Jay¹  Doug Chan² 

[1] Department of Physiology, Tufts University, 136 Harrison Ave, 02111, Boston, MA, USA;Protech Laboratory Inc, 77054, Houston, TX, USA;

关键词: Plasmin;    Wound Healing Assay;    Client Protein;    SUM159 Cell;    OpenLab Software;   

DOI  :  10.1186/1471-2407-10-294

 received in 2009-10-08, accepted in 2010-06-16,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMetastasis is a multi-step process that is responsible for the majority of deaths in cancer patients. Current treatments are not effective in targeting metastasis. The molecular chaperone hsp90α is secreted from invasive cancer cells and activates MMP-2 to enhance invasiveness, required for the first step in metastasis.MethodsWe analyzed the morphology and motility of invasive cancer cells that were treated with exogenous exosomes in the presence or absence of hsp90α. We performed mass spectrometry and immunoprecipitation to identify plasminogen as a potential client protein of extracellular hsp90α. Plasmin activation assays and migration assays were performed to test if plasminogen is activated by extracellular hsp90α and has a role in migration.ResultsWe found that hsp90α is secreted in exosomes in invasive cancer cells and it contributes to their invasive nature. We identified a novel interaction between hsp90α and tissue plasminogen activator that together with annexin II, also found in exosomes, activates plasmin. Extracellular hsp90α promotes plasmin activation as well as increases plasmin dependent cell motility.ConclusionsOur data indicate that hsp90α is released by invasive cancer cells via exosomes and implicates hsp90α in activating plasmin, a second protease that acts in cancer cell invasion.

【 授权许可】

Unknown   
© McCready et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.