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Hsp90

Invasion is a critical process of cancer, which eventually leads to metastasis. During metastasis, cancer cells penetrate the extracellular matrix and lodge elsewhere eventually developing into new tumors.

Until now, scientists believed that heat shock protein90 (hsp90) was primarily an intracellular protein, responsible for folding and function of important cellular proteins such as steroid hormone receptors, protein kinases and proteins controlling the cell cycle and apoptosis. It has only recently been identified as functioning outside the cell and as having a role in invasion.

Fig: Hsp90 3D-model with an inhibitor

Invasive tumors accelerate the degradation of extracellular matrices by matrix metalloproteinases (MMPs). This provides access to the vasculature and lymphatic system, allowing tumor dissemination. Recent studies have shown that hsp90 plays a role in the activation of MMPs outside the cell, thus inhibition of extracellular hsp90a via cell impermeant drugs leads to a reduction of activated MMP2 and corresponding decrease of tumor cell invasiveness.

To date there are no effective and safe treatments against metastases due to the lack of reliable validated drug targets. Extracellular hsp90 is a particularly attractive target for new drug development because it is possible that treatments for cancer based on the inhibition of extracellular hsp90 will be applicable against various forms of cancer.