Control of tumor cell migration in culture medium – focusing on the effects of MMP expression

• Main Authors: Hu Shin Hsin, 胡仕欣
• Other Authors: Hsu Chung-Ping
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/82313947291949844523

碩士 === 國立暨南國際大學 === 生物醫學科技研究所 === 95 === According to the annual report of Department of Health, Executive Yuan, ROC（Taiwan）, cancer has already became the leading cause of the ten major deaths in Taiwan . Lung cancer is the number one cause of cancer death in Taiwan, that it about 70% lung cancer patients whose death was caused by cancer cells metastasis. Tumor metastasis is a complex process involving coordination of matrix disintegration, cell detachment, cell-cell junction disassembly, and cell migration. The process is facilitated by the tumor cells’ ability to degrade their surrounding extracellular matrix (ECM), especially basement membranes lining the blood vessels. Increased degradation of ECM and basement membranes through secretion of ECM-degrading enzymes enables the cells to enter and leave blood vessels. Degradation of basement membranes and ECM is required for tumor cell invasion and metastasis. The incidence of disease and death rate of the thoracic tumor rise sharply, danger degree of Taiwan is on the high more side than that of other country. The lung cancer is in compatriot's cancer ranks, man occupy second, women and rank first. The prognosis situation of lung cancer is usually bad, due to diagnosed at a late stag. Another common tumor of thorax with rapid increase of incidence in recent years is esophageal cancer to ten malignancy in 2006’s report . The extracellular matrix proteinase secreted by malignant cancer cell, including serine proteinase, matrix metalloproteinases (MMP), cathepsins, plasminogen activator, and heparanitase. The MMPs are the key enzymes in the degradation of basement membranes and extracellular matrix. MMPs are a group of cellular matrix proteinase. In human, the MMP family consists of at least 21 different members, which can degrade different type of ECM. The relation between MMP and tumor cell growth, invasion, and metastasis is directly proportional. Proteolytic activity of MMP is inhibited by specific inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMP). Under cancer develop the expression of MMP and TIMP is highly coordinated. Our previous study using immunohistochemical stain has demonstrated occurrence of bone-marrow microinvolvement in more than 30% of the non-small cell lung cancer patients, and more than 40％ of the esophageal cancer patients, respectively. Detected a single tumor cell in bone-marrow is call bone-marrow microinvolvement. Though the occurrence of bone-marrow microinvolvement was not related to patient age, sex, cell type, or TNM stages, subsequent study from our lab demonstrated that existence of BMM itself did not influence the prognosis (p=0.109), however, patients with positive MMP-13 expression had a poorer 5-year survival rate of 26.5% (p=0.025). These data indicate that non-small cell lung cancer cells with MMP-13 expression, despite of BMM status, tend to shed and aggregate in the bone marrow, which is subsequently reflected in a poorer survival rate. The current study will be conducted in the cell culture medium. Using different cell lines, we will analyze the impact of structure and concentration of medium, and growth factor on cell growth. By selecting the most suitable cell lines and growth condition, then we will analyze the expression of MMPs on tumor growth and migration.