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c-Met Mediated Ovarian Cancer Cell Motility

c-Met 介导的卵巢癌细胞运动

基本信息

批准号：
7488529
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
项目类别：
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/7488529
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

项目摘要

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)：在卵巢癌中，与大多数其他实体肿瘤一样，转移性疾病而不是原发病变是大多数患者最常见的死亡原因。细胞迁移的HGF/c-Met信号异常被认为与肿瘤的侵袭和转移有关。因此，针对HGF/c-Met信号转导的特异性抑制剂可能在Met活性导致侵袭/转移表型的癌症治疗中具有重要的治疗潜力。近年来，几种c-Met受体拮抗剂相继问世。这项研究的目的是研究c-Met特异性ATP竞争性小分子SU11274对人卵巢癌细胞运动和跨内皮细胞侵袭的影响。我们假设c-Met介导的信号通过改变为运动提供实际手段的特定物理过程来影响细胞运动。此外，我们怀疑，尽管c-Met的作用因细胞类型不同而不同，但抑制c-Met可能会显著抑制高表达c-Met的卵巢癌细胞的运动和侵袭活性。该项目将通过使用电池-基质阻抗传感(ECIS)来促进，ECIS是一种新型的基于细胞的生物传感器，可以监测附着在小金电极上的细胞的形态变化。这种方法将与我们在荧光成像、ECM涂层聚丙烯酰胺底物和数字图像分析方面的既定能力相结合，以表征对SU11274的各种细胞反应。具体目的是：1.确定c-Met活化对细胞迁移速度和/或定向持续的影响。2.检测活化c-Met对细胞收缩能力和细胞形态的影响。3.探讨SU11274灭活c-Met对卵巢癌细胞内皮细胞侵袭能力的影响。这项研究将为c-Met在人卵巢癌细胞转移行为中的功能作用提供新的信息。这一结果将有助于更广泛的目标，即开发一种新的分子靶向抗癌疗法，用于卵巢癌，可能还包括其他形式的癌症。