TY - JOUR
T1 - Proteolytic imbalance is reversed after therapeutic surgery in breast cancer patients
AU - Giannelli, Gianluigi
AU - Erriquez, Roberta
AU - Fransvea, Emilia
AU - Daniele, Antonella
AU - Trerotoli, Paolo
AU - Schittulli, Francesco
AU - Grano, Maria
AU - Quaranta, Michele
AU - Antonaci, Salvatore
PY - 2004/5/1
Y1 - 2004/5/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Matrix metalloproteases
KW - MMP-2
KW - MMP-9
KW - Therapy
KW - TIMP-1
KW - TIMP-2
UR - http://www.scopus.com/inward/record.url?scp=1642460199&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1642460199&partnerID=8YFLogxK
U2 - 10.1002/ijc.20009
DO - 10.1002/ijc.20009
M3 - Article
C2 - 14999790
AN - SCOPUS:1642460199
VL - 109
SP - 782
EP - 785
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 5
ER -