Daniel Jay, professor of Cellular & Molecular Physiology , published Extracellular Heat Shock Protein (Hsp)70 and Hsp90<alpha> Assist in Matrix Metalloproteinase-2 Activation and Breast Cancer Cell Migration and Invasion in PloS One. This work was published with Tufts co-authors Jessica Sims (phD student) and Jessicia McCready (postdoc). The abstract is below –
Breast cancer is second only to lung cancer in cancer-related deaths in women, and the majority of these deaths are caused by metastases. Obtaining a better understanding of migration and invasion, two early steps in metastasis, is critical for the development of treatments that inhibit breast cancer metastasis. In a functional proteomic screen for proteins required for invasion, extracellular heat shock protein 90 alpha (Hsp90alpha) was identified and shown to activate matrix metalloproteinase 2 (MMP-2). The mechanism of MMP-2 activation by Hsp90alpha is unknown. Intracellular Hsp90alpha commonly functions with a complex of co-chaperones, leading to our hypothesis that Hsp90alpha functions similarly outside of the cell. In this study, we show that a complex of co-chaperones outside of breast cancer cells assists Hsp90alpha mediated activation of MMP-2. We demonstrate that the co-chaperones Hsp70, Hop, Hsp40, and p23 are present outside of breast cancer cells and co-immunoprecipitate with Hsp90alpha in vitro and in breast cancer conditioned media. These co-chaperones also increase the association of Hsp90alpha and MMP-2 in vitro. This co-chaperone complex enhances Hsp90alpha-mediated activation of MMP-2 in vitro, while inhibition of Hsp70 in conditioned media reduces this activation and decreases cancer cell migration and invasion. Together, these findings support a model in which MMP-2 activation by an extracellular co-chaperone complex mediated by Hsp90alpha increases breast cancer cell migration and invasion. Our studies provide insight into a novel pathway for MMP-2 activation and suggest Hsp70 as an additional extracellular target for anti-metastatic drug development.
Daniel has answered some questions about open access.
Please tell us a little about the research that went into this article.
This study addressed the mechanism of how extracellular components regulate breast cancer invasiveness, an important process in cancer spread and metastasis. Jessica Sims identified key molecular chaperones that function in side of cells to activate many proteins, are present outside of cancer cells and function to activate an enyzme called Matrix Metalloproteinase 2, which has been well implicated in cancer invasion.
Why did you choose to publish in an open access journal?
I’ve long believed in open access journals for biomedicine as they have been highly successful in physics. On a practical note, the turnover time was rapid and judgement fair and both of these criteria were important because publishing this work was critical for Jessica’s dissertation.
How do you think open access will impact your field in the future?
I believe that Open access will grow and hope that it attains the same impact it has enjoyed in physics. The value is that all good science will be available and its importance will be judged by how actively it is accessed. It gets away from the current publishing model that can be subject to trends and bias toward popular ideas. I hope that Open access will provide avenues for paradigm shifting work that can have difficulty being published.
Sims, Jessica D., Jessica McCready, Daniel G. Jay “Extracellular Heat Shock Protein (Hsp)70 and Hsp90alpha Assist in Matrix Metalloproteinase-2 Activation and Breast Cancer Cell Migration and Invasion.” PLoS ONE 6, no. 4 (2011). Available from Tufts Digital Library, Digital Collections and Archives, Medford, MA. http://hdl.handle.net/10427/71568
As of 4/4/2013 this open access article has been cited 24 times per Google Scholar.