c-Met Mediated Ovarian Cancer Cell Motility

c-Met 介导的卵巢癌细胞运动

• 批准号: 7322093
• 负责人: Chun-Min Lo
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7322093
• 关键词: Affect; Behavior; Biochemical; Biological Assay; Biosensor; Cause of Death; Cell Line; Cells; Dimethyl Sulfoxide; Disease; Electrodes; Epithelial Cells; Extracellular Matrix; Extracellular Space; Goals; Gold; Hand; Human; Image Analysis; In Vitro; Invasive; Investigation; Location; Malignant Epithelial Cell; Malignant Neoplasms; Malignant neoplasm of ovary; Measurement; Measures; Mediating; Microscopic; Monitor; Morphology; Movement; Neoplasm Metastasis; Normal Cell; Ovarian; Ovarian Carcinoma; Pathway interactions; Patients; Phenotype; Primary Lesion; Rate; Regulation; Research; Role; Signal Pathway; Signal Transduction; Solid Neoplasm; Speed; Stress; Surface; Text; Therapeutic; Time; Traction; Tumor Cell Invasion; Video Microscopy; base; cancer cell; cancer therapy; cell behavior; cell motility; cell type; digital imaging; electric impedance; fluorescence imaging; inhibitor/antagonist; migration; monolayer; novel; physical process; polyacrylamide; receptor; response; small molecule; wound

DESCRIPTION (provided by applicant): In ovarian cancer, as in most other solid tumor, metastatic disease rather than the primary lesion is the most common cause of death of the majority of patients. Dysregulated HGF/c-Met signaling of cell migration has been suggested to contribute to tumor invasion and metastasis. Specific inhibitors against HGF/c-Met signaling, therefore, may have important therapeutic potential for the treatment of cancers in which Met activity contributes to the invasive/metastatic phenotype. Recently, several c-Met receptor antagonists have been developed. The goal of the proposed research is to investigate the effects of a c-Met specific ATP-competitive small-molecule SU11274 on human ovarian carcinoma cell motility and transendothelial invasion. We hypothesize that c-Met- mediated signals affect cell motility by altering specific physical processes which provide the actual means for movement. Moreover, we suspect that although the role of c-Met varies from cell type to cell type, inhibition of c-Met may significantly inhibit motility and invasive activity in ovarian cancer cells expressing high levels of activated c-Met. The project will be facilitated by the use of electric cell-substrate impedance sensing (ECIS), a novel cell-based biosensor that monitors morphological changes of cells adherent on small gold electrodes. This approach will be combined with our established ability in fluorescence imaging, ECM coated polyacrylamide substrate, and digital image analysis to characterize a variety of cellular responses to SU11274. The specific aims are: 1. To determine the effect of activated c-Met on cell migration speed and/or directional persistence. 2. To determine the effect of activated c-Met on cell contractile force and morphology. 3. To determine the effect of c-Met inactivation by SU11274 on the transendothelial invasion of ovarian cancer cells. The proposed research will provide new information regarding the functional role of activated c- Met in metastatic behaviors of human ovarian carcinoma cells. The results will contribute to a broader goal of developing a new molecularly targeted anti-cancer therapy for ovarian cancer and possibly other forms of cancer.

描述（由申请人提供）：