Gastric cancer - The role of matrix metalloproteinases in tumor progression

Gastric cancer (GC) is a very aggressive malignant tumor of gastrointestinal tract due to its invasive nature and early metastatic ability. Degradation of the extracellular matrix (ECM) and basement membrane (BM) barriers are essential steps in the pathology of GC. Matrix metalloproteinases (MMPs) play a crucial role in the process due to their ability to degrade and rearrange these barriers to support and facilitate tumor cell migration. Therefore, these enzymes affect early carcinogenesis, tumor development and growth as well as the invasion of cancer cells at primary and metastatic sites. The endogenous inhibitors of matrix metalloproteinases (TIMPs) inhibit the active forms of MMPs and regulate the processes of their activation. The imbalance between MMPs and TIMPs may facilitate the progression of neoplastic cells. The enhanced levels of various MMPs and TIMPs have been observed in the tissue, plasma and serum of patients with many types of tumor, including gastric cancer. Moreover, levels of MMPs and TIMPs in the tissues as well as in the blood of GC patients correlated with tumor stage, depth of tumor invasion, presence of nodal and distant metastases. Selected MMPs and their tissue inhibitors were proved to be independent prognostic factors for GC patients' survival. However, further studies concerning the role of MMPs and their inhibitors in tumor biology are necessary. (C) 2011 Elsevier B.V. All rights reserved.