The prognostic value of MMP-9 expression in lung adenocarcinoma

www.onk.ns.ac.rs/Archive Vol 21, No. 3-4, December 2013 INTRODUCTION Lung cancer is one of the leading causes of death throughout the world. Approximately one million people, 850,000 men and 330,000 women, die of lung cancer per year (1). Despite some advances in the diagnosis and treatment of lung cancer in the last several decades, the prognosis of lung cancer remains poor. The overall 5-year survival rate of lung cancer is approximately 12.4% of all newly detected cases in the world, and <9% in developing countries (2, 3). The MMP family comprises 23 human enzymes that traditionally have long been associated with cancer invasion and metastasis because of their ability to degrade the extracellular matrix. However, recent studies have showed that the roles of MMPs in tumour development and metastasis are much more complex than was originally envisioned. In vitro and animal studies have demonstrated that MMPs are also the key mediators of growth factor activation, bioavailability and receptor signalling, cell adhesion and motility, apoptosis and survival mechanisms, angiogenesis, and inflammatory responses and immune surveillance (4). Matrix metalloproteinases (MMP) are the group of enzymes responsible for degradation of certain extracellular matrix proteins such as collagen, proteoglycan, elastin, laminin and fibronectin. Malignant diseases are accompanied with higher expression of matrix metalloproteinases and lower concentrations of the tissue inhibitors of matrix metalloproteinases (TIMP), also resulting in an increased proteolytic activity. The presence of matrix metalloproteinases was discovered on the surface of invasive tumor cells (5). Degradation of the basal membrane and extracellular matrix presents the key step in the process of intravasation and extravasation of tumor cells (6). MMP-9 belongs to the gelatinases group, synthesized by keratinocytes, monocytes, alveolar macrophages, polymorphonuclear neutrophil granulocytes, and in many cancer cells. Tumor invasion is a multi-phase process in which the cell motility is associated with controlled proteolysis and includes interaction between tumor cells and extracellular matrix. During the invasion process, malignant tumor cells are detached from the primary tumor, migrate through structural barriers such as the basal membrane and surrounding extracellular matrix rich in collagen. Degradation of the stromal extracellular matrix is also considered one of the key steps in the process of tumor angiogenesis (7). It has been proved that the activity of matrix metalloproteinases is necessary for increased motility of epithelial cells, as well as for the growth of metastatic deposits. Research has confirmed that MMP-2 and MMP-9 have an exceptionally significant role in metastasizing, due to their ability to degrade type IV The prognostic value of mmp-9 expression in lung adenocarcinoma