ABSTRACT
Matrix metalloproteinases [MMPs] and their inhibitors [TIMPs] modulate ECM composition and may affect breast cancer invasion and metastases. Bone metastases are a frequent complication of advanced breast cancer. This work investigated the relationship between plasma levels of MMP-9, TIMP1, PTHrP, tissue expression of CD44v6 and the development of nodal and bone metastases in 40 female patients with different stages of breast cancer. The control group comprised 10 females with benign breast lesions. All studied parameters were significantly higher in patients than in controls. Patients with lymph node involvement has significantly higher plasma MMP-9, MMP9/TIMP-1 ratio and CD44c6 expression than those without nodal affection, [p= 0.018, 0.006 and 0.02 respectively]. Higher MMP-9 MMP9/TIMP-1 ratio and PTHrP were found in patients with than those without bone metastases [p = 0.013, 0.01 and 0.0002 respectively]. CD44v6 expression was associated with increased MMP-9 and TIMP-1 levels as well as higher tumour grade. Post-operative MMP-9 was significantly lower than pre-operatively. Our data indicate that increased plasma MMP-9 and MMP-9 / TIMP-1 imbalance may be useful markers for development of nodal and bone meatstases in breast cancer patients and in predicting post-operative recurrence. While CD44v6 is involved in nodal metastases, PTHrP seems to be an important determinant of development of bone secondaries