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Proj 2: Molecular Imaging of Cell Surface Receptors in Cancer

项目 2：癌症细胞表面受体的分子成像

基本信息

批准号：
7490305
负责人：
Alnawaz Rehemtulla
金额：
$ 27.65万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7490305
关键词：
Affect Animals Apoptosis Behavior Biochemical Biological Assay Blood Vessels Bone Marrow Breast CXCR4 Receptors CXCR4 gene Cancer Etiology Cell Proliferation Cell Surface Receptors Cells Cellular Assay Class Clinical Communications Media Condition Cultured Cells Development Dose Environment Enzymes Epidermal Growth Factor Receptor Epithelial Event Exhibits Growth Growth Factor Head and neck structure Hepatocyte Growth Factor Human Image In Vitro Invasive Life Ligand Binding Ligands Link Liver Lung Malignant Neoplasms Mediating Membrane Modeling Molecular Monitor Mus Mutation Nature Neoplasm Metastasis Noise Numbers Oncogenes Organ Outcome Pharmaceutical Preparations Phenotype Phosphotransferases Physiological Physiological Processes Play Protein Overexpression Protein Tyrosine Kinase Proto-Oncogene Protein c-met Public Health Purpose Receptor Activation Receptor Inhibition Recruitment Activity Reporter Reporting Role Sensitivity and Specificity Signal Transduction Signaling Molecule Site Solid Neoplasm Specificity Stem cells Stromal Cell-Derived Factor 1 System Tail Testing Therapeutic Therapeutic Agents Therapeutic Intervention Treatment Efficacy Xenograft Model angiogenesis autocrine base cancer cell cancer site cancer therapy cell transformation chemokine extracellular human MET protein kinase inhibitor migration molecular imaging mouse model neoplastic cell neutralizing antibody novel paracrine receptor response small molecule stable cell line tumor tumor xenograft tumorigenesis validation studies

项目摘要

PROJECT 2: Cell surface receptors comprise an important class of membrane molecules that form communication links between the extracellular milieu and the cell's interior. In addition, a number of cell surface receptors have been shown to play a significant role in imparting specific phenotypes to transformed cells, for example growth factor independence and metastatic behavior. Non-invasive imaging of receptor activity dynamically in live cells and mouse models would significantly enhance our understanding of the role of these receptors in the etiology of cancer and the response of tumors to therapeutic agents directed against these receptors. For the purpose of this proposal we will focus on three distinct receptors. The epidermal growth factor receptor (EGFR) is often over-expressed and activated in tumors in a ligand independent manner, while the hepatocyte growth factor receptor (Met) is activated in an autocrine manner in that tumor cells express the ligand (HGF) and the receptor (Met) simultaneously thus constitutively activating intracellular signaling cascades. The CXCR7 receptor is activated in a paracrine manner in that specific organs such as bone marrow, lung and liver express SDF, the ligand which through CXCR7 activation results in the spread and growth of metastasis to these sites. In Project 2, we propose to develop molecular imaging strategies to image activity of three receptors that contribute significantly to the transformed phenotype. The proposal is organized in three aims, one for each of the above three receptors. In each of the aims we will develop two independent approaches to image the receptor and the one with the best signal to noise and specificity will be used in further in-vitro validation studies to demonstrate that the reporter faithfully reports on the appropriate molecular events. Lastly, in each of the aims, the appropriate receptor will be used to investigate the efficacy of novel therapies directed against each receptor in a live mouse model and the efficacy of the therapy will be correlated with molecular imaging as a non-invasive surrogate for receptor activity. Public Health: The studies proposed here will result in the development of imaging based mouse models that will facilitate the development and testing of anti-cancer therapies directed against key receptor molecules.

项目2：细胞表面受体构成了一类重要的膜分子