Role and Utility of Annexins in Endothelium of Solid Tum

膜联蛋白在实体肿瘤内皮细胞中的作用和用途

基本信息

批准号：
7265209
负责人：
Jan Eugeniusz Schnitzer
金额：
$ 40.3万
依托单位：
SIDNEY KIMMEL CANCER CENTER
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-23 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7265209
关键词：
Ablation Actins Address Adult Affect Aftercare Anesthesia procedures Angiogenic Factor Animals Annexins Anterior Pituitary Gland Antibodies Apoptosis Apoptotic Area Attention Autoradiography Back Backcrossings Beds Binding Biochemical Biological Assay Biological Models Biostatistics Core Blocking Antibodies Blood Blood Vessels Blood capillaries Brain Breast Breast Adenocarcinoma Breast Carcinoma Caliber Caveolae Caveolins Cell Line Cell Proliferation Cell membrane Cell physiology Cell surface Cells Chemicals Clathrin Clinical Coagulation Process Collaborations Color Complex Computer software Condition Confocal Microscopy Congenic Mice Congenic Strain Conscious Consult Consultations Contracts Contralateral Cryoultramicrotomy Culture Media Cultured Cells Cytosol Data Defect Dermis Detection Development Dexamethasone Disease regression Doctor of Medicine Dorsal Dyes Early Diagnosis Electron Microscopy Endothelial Cells Endothelium Ensure Environment Enzyme-Linked Immunosorbent Assay Epidermis Evaluation Exhibits Exposure to Factor V Fatty acid glycerol esters Feedback Fibrin Fibroblast Growth Factor Fibroblast Growth Factor 2 Fibroblasts Fibronectins Flowers Fluorescence Formazans Funding Gene Expression Generations Granulation Tissue Growth Growth Factor Harvest Healed Hepatocyte Growth Factor Histocompatibility Testing Histological Techniques Homing Horseradish Hour Housing Human Human Resources Image Imagery Immunofluorescence Immunologic Immunoglobulin M Immunohistochemistry Immunotherapy Immunotoxins Implant In Situ Nick-End Labeling In Vitro Incubated Indium Individual Injection of therapeutic agent Institutes Instruction Insulin-Like Growth Factor I Interleukin-1 Interleukin-8 Intracellular Membranes Invaded Invasive Investigation Knock-out Knockout Mice Knowledge Label Length Lesion Lewis Lung Carcinoma Light Limb structure Literature Liver Localized Location Logistics London Lung Lung Neoplasms Malignant - descriptor Malignant Epithelial Cell Malignant neoplasm of prostate Mammary gland Measures Mediating Membrane Messenger RNA Metastatic Lesion Metastatic Neoplasm to the Lung Methodology Methods Microscope Microscopic Microscopy Migration Assay Modality Modeling Molecular Molecular Probes Monitor Monoclonal Antibodies Mouse Mammary Tumor Virus Mus Nature Necrosis Neoplasm Metastasis Neoplasms in Vascular Tissue Normal tissue morphology Numbers Organ Palpable Pan Genus Partner in relationship Pathway interactions Patients Phenotype Phosphatidylserines Phospholipids Physiologic Neovascularization Physiological Pituitary Gland Placental Growth Factor Platelet-Derived Growth Factor Play Polyoma Virus Middle T Staining Method Positron-Emission Tomography Preparation Principal Investigator Process Proliferating Promega Prostate carcinoma Proteins Proteomics Protocols documentation Published Comment Radio Range Rate Rattus Reaction Reader Reading Recombinants Relative (related person)Renal Cell Carcinoma Reporter Reporting Research Institute Research Personnel Resolution Review Committee Risk Role Running Serum-Free Culture Media Side Signal Transduction Silicon Dioxide Site Site Visit Skin Small Interfering RNA Smooth Muscle Myocytes Solid Solid Neoplasm Solutions Somatomedins Specificity Speed Staging Staining method Stains Standards of Weights and Measures Statistical Data Interpretation Stimulus Stress Structure Suggestion Surface Surgical incisions System TNF gene Techniques Technology Testing Tetrazolium Therapeutic Thick Time Tissue Stains Tissues Transfection Transforming Growth Factors Transgenic Mice Transgenic Model Transgenic Organisms Tube Tumor Angiogenesis Tumor Necrosis Factor-alpha Tumor Necrosis Factors Tumor Volume Tumor-Associated Process Tumor-Associated Vasculature Universities Variant Vascular Endothelial Cell Vascular Endothelial Growth Factors Vascularization Video Microscopy Viral Tumor Antigens Week Wild Type Mouse Work Wound Healing angiogenesis aqueous base bone cadherin 5 calcein AM cancer therapy capillary caveolin 1 cell fixation cell growth cell motility cell type charge coupled device camera chorioallantoic membrane congenic breeding culture plates day density esterase experience fluorexon fluorophore gel electrophoresis healing human TNF protein implantation improved in vitro Assay in vivo in vivo Model innovation intravital microscopy knock-down lung Carcinoma macrophage matrigel metaplastic cell transformation migration monolayer mouse model neoplastic cell neovascularization novel novel diagnostics novel strategies oxidation planetary Atmosphere preference prevent programs promoter protein expression protein function receptor research study sample fixation scalpel sialosyl-T antigen size stellate cell subcutaneous tissue culture tumor tumor growth tumor progression vasculogenesis whole body imaging wound

项目摘要

The broad focus of this project is to understand the molecular mechanisms underlying the effects of the tumor microenviroment on endothelial function and the effects of specific tumor-induced endothelial cell proteins on tumor growth, progression and angiogenesis. Such basic information is essential to develop new diagnostic and therapeutic strategies that may prove useful in improving the early detection and treatment of solid t umors. W e w ill focus p rimarily one haracterizing our new tumor-induced, endothelial and caveolar target, an AnnAl related protein, identified through our proteomic analysis of tumor luminal endothelial cell membranes. We will define the specific nature and function of this protein as well as use our panel of specific antibodies to this new target protein to evaluate expression and function in the context of solid tumors and its endothelium. To this end, we will address the following specific aims: 1. To determine the role of the tumor cell and tissue host environment, including specific angiogenic factors, on its expression, translocation, and externalization in caveolae. 2. To investigate the role of its expression by the tumor endothelium on endothelial cell function, solid tumor growth, and angiogenesis. We will use various rat and mouse tumor model systems as well as multiple biochemical and microscopic methodologies to examine in vivo and in cell culture the function of specific expression in caveolae. For instance, the potential anti-tumor effects of naked antibodies blocking possible protein function will be assessed. With this information, we plan to develop the means to improve the detection and staging of solid tumors as well as elaborate novel strategies for more effective and less toxic anti-cancer treatments.

该项目的主要重点是了解肿瘤微环境对内皮功能影响的分子机制以及特定肿瘤诱导的内皮细胞蛋白对肿瘤生长、进展和血管生成的影响。这些基本信息对于开发新的诊断和治疗策略至关重要，这些策略可能有助于改善实体瘤的早期检测和治疗。我们将主要关注表征我们新的肿瘤诱导的内皮和细胞小穴靶标，这是一种 AnnAl 相关蛋白，通过我们对肿瘤管腔内皮细胞的蛋白质组学分析来鉴定膜。我们将定义这种蛋白质的具体性质和功能，并使用我们针对这种新靶蛋白的特异性抗体组来评估实体瘤及其内皮细胞中的表达和功能。为此，我们将实现以下具体目标： 1. 确定肿瘤细胞和组织宿主环境（包括特定的血管生成因子）对其在小凹中的表达、易位和外化的作用。 2. 探讨肿瘤内皮表达其对内皮细胞功能、实体瘤生长和血管生成的作用。我们将使用各种大鼠和小鼠肿瘤模型系统以及多种生化和显微镜方法来检查体内和细胞内培养小凹中特定表达的功能。例如，将评估裸露抗体阻断可能的蛋白质功能的潜在抗肿瘤作用。有了这些信息，我们计划开发改进实体瘤检测和分期的方法，并制定更有效、毒性更低的抗癌治疗的新策略。