What: Tufts University researchers and colleagues have discovered an extracellular form of heat shock protein 90 (hsp90) and shown its role in cancer invasion.
Where: Published in Nature Cell Biology – Volume 6, 2004
When: June, 2004
Why: Invasion is a key step in tumor progression that eventually leads to metastases when a disseminated tumor cell penetrates through the extracellular matrix and establishes a secondary tumor site elsewhere.
To date there are no effective and safe treatments against metastases due to the lack of reliable validated drug targets. Hsp90 recently has gained significant attention as an important target for cancer therapeutics and hsp90 inhibitors are currently in Phase I and II clinical trials. Since hsp90 is also a key protein for normal cell function, there is some concern about treatment-related toxicity, especially if hsp90 inhibitors are unable to distinguish normal and cancer cells.
In the published article entitled "Functional Proteomic Screens Reveal an Essential Extracellular Role for Hsp90a in Cancer Cell Invasiveness," the researchers used a functional screen on the cell surface proteome of a highly invasive human tumor cell line. The screen identified the extracellular hsp90 associated with tumor cell invasion.
The researchers demonstrated a direct physical and functional interaction between hsp90 and matrix metalloproteinase 2 (MMP2), a primary player in the tumor invasion process. This opens the possibility for developing antibodies against hsp90 for the treatment of cancer.
"This work highlights the relevance of validating function at the protein level. Genetic approaches would have missed the discovery of the novel mechanism of hsp90 action" said Daniel Jay, Ph.D., Professor at Tufts University School of Medicine and senior author of the paper. "These results indicate a role for a functional proteomic approach in addition to genetic screens and suggest anti-hsp90 antibodies may be potential options for cancer treatment."
Jay and colleagues collaborated with scientists at the National Cancer Institute and Xerion-Pharmaceuticals AG of Germany on this research.
For more information, a copy of the article or interviews with the authors, please contact Peggy Hayes, Tufts University Health Sciences Public Relations, 617-636-3707 or peggy.hayes@tufts.edu or Siobhan Gallagher, 617-636-6586 or siobhan.gallagher@tufts.edu.
Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences are international leaders in innovative medical education and advanced research. The School of Medicine is renowned for excellence in education in general medicine, special combined-degree programs in business, health management, public health, bioengineering and international relations; as well as its basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the school is affiliated with four major teaching hospitals and over 30 health care facilities. The Sackler School undertakes research that is consistently rated among the highest in the nation for its impact on the advancement of medical science.
Journal
Nature Cell Biology