Interleukin-6 induces secretion of tissue inhibitors of etalloproteinases by breast carcinoma cells.

Interleukin (IL)-6 can induce matrix metalloproteinases (MMPs) expression, which may be critical factors involved in tumor metastasis. Tissue inhibitors of metalloproteinases (TIMPs) are important inhibitory enzymes of MMP. This study was designed to investigate the effect of recombinant IL-6 on the MMP/TIMP expression in MDA-MB-231 breast cancer cell line in a dose dependent manner (10, 25 and 50ng/ml) in comparison to non-treated breast cancer cells (control). The data demonstrated that low dose (10 ng/ml) of IL-6 failed to induce TIMP-1 and -2 production by breast cancer cells compared to control cells whereas moderate (25 ng/ml) and high (50ng/ml) exposure levels promoted a significant expression of TIMP-1 (P<0.01 and P<0.0001) respectively as compared to control cells. TIMP-2 was significantly released (P<0.0001) from breast cancer cells higher than in control cells at moderate and high exposure levels of IL-6. This up-regulation of TIMP-1 and -2 was accompanied with undetectable levels of MMP-1, -2, -3, -8, -9, -10, and -13. Furthermore, IL-6 potentially increased the invasion potency of cancer cells significantly (P<0.05 and P<0.01) at moderate and high exposure levels respectively. These findings suggest that IL-6 could promote the invasion potency of breast cancer cells by inducing secretion of TIMP-1 and -2, causing a disturbance in TIMP/MMP balance.