Invasion and metastases in gastric cancer: In vitro and in vivo models with clinical correlations

The major obstacle towards improved survival from gastric cancer is in the development of metastatic disease. Techniques in cellular and molecular biology have now advanced to the point to allow an examination of specific biomolecules in processes related to gastric cancer cell invasion through the basement membrane of blood vessels or lymphatics (eg, the first step in developing metastatic disease). Identification of such biomolecules in primary gastric cancer has been enhanced by the establishment of primary human gastric cancer cell lines. These cell lines, named SK-GT for Sloan- Kettering gastric tumor, have provided the basis for a detailed analysis of the invasive phenotype of gastric cancer cells and has resulted in the identification of potentially important prognostic biomarkers. These molecular studies have revealed that in gastric cancer cells there exists a series of integrated biomolecules that are intimately involved in processes related to tumor cell invasion. Included among these are proteins associated with attachment to the basement membrane (ie, laminin receptor) as well as with proteolysis of the basement membrane (ie, matrix metalloproteinase-2, MMP-2). These factors, as well as others, have been clinically evaluated for their prognostic significance in patients with resected, primary gastric cancer. These clinical studies indicate that overexpression of factors associated with the invasion of gastric cancer cells through the basement membrane, including E-cadherin, MMP-2, plasminogen activator inhibitor-I (PAI-I), and tissue inhibitor metalloproteinase-2 (TIMP-2), can be predictive of tumor recurrence and overall survival in patients with this disease.