Matrix metalloproteinases and their tissue inhibitors - Expression, role and regulation in human malignant non-Hodgkin's lymphomas

Human malignant non-Hodgkin's lymphomas (NHL) represent a heterogeneous gro up of neoplasms, which vary in their clinical behavior and pathophysiology. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been shown to play a role in the pathophysiology and clinical aggressivenes s of human NHL. In this setting, MMP-9 and TIMP-1 appear to be the most imp ortant members of the MMP and TIMP families, and overexpression of both cor relates with a poor clinical outcome of patients with NHL. MMP-9 and TIMP-1 , however, act through different mechanisms and are produced by different c ell types. Expression of both is upregulated by interleukin-6 (IL-6), a cyt okine that is known as one of the factors involved in the pathophysiology o f human NHL. In this review we summarize the complex regulation of MMP and TIMP expression in human NHL and propose a mechanism by which MMP-9, TIMP-1 and IL-6 may influence the biology of these tumors.