Proteolytic imbalance is reversed after therapeutic surgery in breast cancer patients

The occurrence of metastasis severely affects prognosis and survival of breast cancer patients. In order to metastasize, breast cancer cells need to cross the basement membrane (BM) tissue boundaries. Matrix metalloproteases (MMPs) are enzymes with proteolytic activity towards extracellular matrix components (ECM) of the BM, that are blocked by physiological tissue inhibitors (TIMPs). Cancer metastasis occurs as a result of an imbalance between MMPs, in particular MMP-2 and MMP-9, and TIMPs, in particular TIMP-2 and TIMP-1. This is the first study to report that pro-MMP-9 and TIMP-1 serum concentrations are inversely correlated in breast cancer patients. In the same patients, we determined the pro-MMP-9, the TIMP-1, the pro-MMP-2 and TIMP-2 before and after surgical eradication of the breast cancer. Our results show that after surgery, when the breast cancer tissue was removed, pro-MMP-9 concentrations dramatically decreased and TIMP-1 concentrations strongly increased, with statistically significant differences, so that a new balance was established. No statistically significant differences were observed regarding pro-MMP-2 and TIMP-2. Also, no correlation was found between pro-MMP-2, pro-MMP-9, TIMP-1 and TIMP-2 and a number of clinical and pathological parameters. In conclusion, our study suggests that pro-MMP-9 and TIMP-1 could be used as markers of disease during the follow-up of breast cancer patients and possibly as prognostic markers, although more studies are needed to address this issue.