ErbB1 and ErbB2 Roles in Invasion and Intravasation

ErbB1 和 ErbB2 在侵袭和内渗中的作用

基本信息

批准号：
7534105
负责人：
JEFFREY E SEGALL
金额：
$ 22.21万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
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：
2008-06-01 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7534105
关键词：
Acute Address Apoptosis Blood Vessels Breast Cancer Cell Breast Cancer Model CSF1 gene CXCL12 gene CXCR4 Receptors CXCR4 gene Cancer Patient Cancer cell line Cell Line Cells Characteristics Chemotaxis Clinical Trials Data Defect EGF gene ERBB2 gene Elements Epidermal Growth Factor Receptor Evaluation Family member Fibroblasts Funding Gene Expression Profile Genes Growth Growth Factor Receptors Heregulin Image In Situ In Vitro Invaded Label Ligands Measurement Mediating Modeling Molecular Profiling Motion Neoplasm Metastasis Numbers Pathway interactions Primary Neoplasm Progress Reports Proteins Relative (related person)Role Signal Pathway Signal Transduction Source Stromal Cell-Derived Factor 1 Stromal Cells Transgenic Model Tyrosine Work Xenograft Model cancer invasiveness cell motility cell type chemokine improved in vivo interest macrophage malignant breast neoplasm neoplastic cell novel paracrine programs receptor response tumor tumor growth tumorigenesis

项目摘要

The broad, long-term objectives of this project are to determine the contributions of ErbBt (EGFR/HER1) and related molecule ErbB2 (HER2/neu) to breast cancer invasiveness, intravasation and metastasis. The contributions of these molecules to tumor cell motility and invasion rather than growth could be significant and not addressed by normal clinical trials. There are three specific aims that will evaluate particular aspects of the contributions of ErbB1 and ErbB2 to invasion and intravasation. The first aim will examine the possible activation of the EGF/CSF1 paracrine loop by other receptor/ligand pairs besides just EGF and CSF1 and the involvement of other stromal cells. The second aim will explore in more detail the elements of the ErbB2 molecule that contribute to invasion and metastasis. The third aim will compare the contributions of specific molecules to in vivo invasion and intravasation. These objective will be achieved using a variety of breast cancer models including breast cancer cell lines, transgenic models of breast cancer, and xenograft models of patient cancer. In vivo invasion measurements will be made using imposed ligand sources. Multiphoton imaging of multiple cell types using fluorescent protein labeling will define the relationships and motion of both tumor and stromal cells in the primary tumor microenvironment. The relevance of this work is in improving our understanding of how breast cancer spreads away from the primary tumor. By identifying the mechanisms by which tumor cells can move out from the primary tumor and enter blood vessels, we hope to identify new ways in which metastasis can be attacked.

该项目的广泛、长期目标是确定 ErbBt (EGFR/HER1) 的贡献以及相关分子ErbB2 (HER2/neu)与乳腺癌侵袭、内渗和转移的关系。这这些分子对肿瘤细胞运动和侵袭而不是生长的贡献可能是显着的正常的临床试验没有解决这个问题。三个具体目标将评估特定方面 ErbB1 和 ErbB2 对侵袭和内渗的贡献。第一个目标将检查除了 EGF 之外，其他受体/配体对也可能激活 EGF/CSF1 旁分泌环 CSF1 和其他基质细胞的参与。第二个目标将更详细地探讨以下要素：有助于侵袭和转移的 ErbB2 分子。第三个目标将比较贡献特定分子对体内侵袭和内渗的影响。这些目标将通过多种方式实现乳腺癌模型，包括乳腺癌细胞系、乳腺癌转基因模型和异种移植模型癌症患者模型。将使用强加的配体源进行体内侵入测量。使用荧光蛋白标记对多种细胞类型进行多光子成像将定义这些关系和肿瘤和基质细胞在原发肿瘤微环境中的运动。这项工作的相关性是提高我们对乳腺癌如何从原发肿瘤扩散的理解。通过识别肿瘤细胞从原发肿瘤移出并进入血管的机制，我们希望找到攻击转移的新方法。