Isoflavone Research Initiative

Tumour growth is not an isolated event, but occurs in tissue already occupied by healthy cells. This healthy tissue is embedded in an extracellular matrix. In order to create space for an emigration of metastases and/or for tumour growth the extracellular matrix must first be degraded. The degradation requires proteases. Consequently, the matrixmetalloproteases (MMPs) are important therapeutic targets for tumour prevention and treatment. The effect of MMPs on the extracellular matrix facilitates cell growth, cell division, migration and invasion of cancer cells, and angiogenesis (Farina et al. 2006).
 
The activity of the MMPs is modulated by enzymes such as protein kinase or tyrosine kinase, and by nuclear factors such as NF-κB. Increased amounts of MMPs are liberated from tumours. E.g., in mice with breast cancer MMP-9 is elevated (Owen et al. 2008).
 
Inhibitors of protein kinase lead to an increased formation of MMPs. In contrast, inhibition of tyrosine kinase leads to reduced formation of MMP-9 in cancer tissue. This effect has been demonstrated in mice with genistein, an inhibitor of tyrosine kinase (Owen et al. 2008). Inhibitors of NF-κB likewise suppress formation of MMP-9 in mice with breast cancer (Owen et al. 2008).

References

Farina, H. G., Pomies, M., Alonso, D. F., and Gomez, D. E. (2006). Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer. Oncol. Rep. 16 (4): 885-891.

Owen, J. L., Torroella-Kouri, M., and Iragavarapu-Charyulu, V. (2008). Molecular events involved in the increased expression of matrix metalloproteinase-9 by T lymphocytes of mammary tumor-bearing mice. Int. J. Mol. Med 21 (1): 125-134.