ErbB1 and ErbB2 Roles in Invasion and Intravasation

该项目的广泛、长期目标是确定ErbBt的贡献(EGFR/HER1) 及其相关分子ErbB2(HER2/neu)与乳腺癌的侵袭、侵袭和转移有关。这个 这些分子对肿瘤细胞的运动和侵袭而不是生长的贡献可能是显著的。 而正常的临床试验并没有解决这一问题。有三个具体目标将评估特定的方面 ErbB1和ErbB2在侵袭和血管内的作用。第一个目标将检查 除EGF和CSF1外，其他受体/配体对可能激活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 参与侵袭和转移的ErbB2分子。第三个目标将比较这些贡献 特定分子对体内侵袭和血管内渗的影响。这些目标将通过各种方式实现 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 病人癌症的模型。体内侵袭测量将使用强加的配基来源进行。 使用荧光蛋白标记的多种细胞类型的多光子成像将定义这些关系和 肿瘤和间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向外扩散的理解。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 希望找出可以攻击转移的新方法。

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.