Application of PPG Technology and Previous Results to Human Breast Tumors

在上一个供资期的项目4中，具体目标2和3导致发现了一个 大鼠和小鼠乳腺肿瘤中的侵袭信号。因此，花费了大量精力来确定 侵袭信号与转移性癌症的趋化性迁移行为的特殊相关性 细胞在小鼠乳腺肿瘤中的侵袭和内渗。我们发现， 导致ZBP 1/mRNA靶向、cofilin、Mena/加帽蛋白和N-WASP/Arp 2/3的途径 在侵袭过程中调节EMT和β-肌动蛋白聚合的途径，以及细胞的方向性 在对EGF的趋化过程中，突起和收缩性受到协调调节。协调调节 这些基因与肿瘤微环境对转移的贡献特别相关， 对血管的趋化性涉及癌细胞从原发性乳腺肿瘤中逃逸。的 在项目4中研究了源自PI 3 K的ZBP 1、cofilin、Mena和N-WASP途径， 所有的核心，他们的能力，改变转移的结果和结果证实了重要性， 乳腺肿瘤转移中的侵袭信号。这一确认激发了对这些问题的详细分析。 这些研究对肿瘤细胞的趋化性和侵袭性产生了新的认识， 转移过程中趋化性的分子机制。入侵信号还包含一个转移 抑制途径，ZBP 1/mRNA靶向途径，有助于cadheren连接稳定性 和抑制EMT从这些研究中出现的一个主要见解是，PI 3 K是起点， 表明其在肿瘤细胞迁移中的重要性， 目前的项目4，这一竞争的更新。 项目5也是从这项工作发展而来的。项目5的主题是推广新技术， 研究结果的前一个资金期在大鼠和小鼠对人类乳腺肿瘤，以确定是否 人类肿瘤中存在的微环境与之前在大鼠和小鼠中发现的微环境相似， 资金周期，以及它们是否可以用作与生物标志物相关的标志，以预测结果。 结合多光子定义的标志和分子病理学研究与生物标志物来源于 前一个资助期的入侵签名，主基因的预后价值将被确定 for human人类breast乳腺cancer癌症.此外，我们感兴趣的是确定入侵签名是否存在于 人类，类似于大鼠和小鼠，含有可用作生物标志物的主基因， 预测人类患者的结果。

In Project 4 during the previous funding period, specific aims 2 and 3- led to the discovery of an Invasion Signature in rat and mouse mammary tumors. As a result, significant effort was expended to define the particular relevance of the Invasion Signature to the chemotactic migratory behavior of metastatic cancer cells during invasion and intravasation in mouse mammary tumors. We found that the genes coding for pathways leading to the ZBP1/mRNA targeting, cofilin, Mena/capping protein and N-WASP/Arp2/3 pathways, that regulate EMT and beta-actin polymerization during invasion, and the directionality of cell protrusion and contractility during chemotaxis to EGF, are coordinately regulated. Coordinate regulation of these genes is particularly relevant to the contribution of the tumor microenvironment to metastasis because chemotaxis to blood vessels is involved in the escape of cancer cells from primary mammary tumors. The ZBP1, cofilin, Mena and N-WASP pathways, emanating from PI3K, were studied in Project 4, with the help of all Cores, for their ability to alter metastatic outcome and the results confirmed the importance of the Invasion Signature in metastasis in mammary tumors. This confirmation stimulated detailed analysis of these pathways in chemotaxis and invasion of tumor cells and these studies have generated new insights into the molecular mechanisms of chemotaxis during metastasis. The Invasion Signature also contains a metastasis suppressor pathway, the ZBP1/mRNA targeting pathway, which contributes to cadheren junction stability and suppression of EMT. A major insight to emerge from these studies was that PI3K is the starting point from which these pathways emanate indicating its critical importance in tumor cell migration leading to the current Project 4 of this competing renewal. Project 5 also evolved from this work. The theme of Project 5 is to extend the new technologies and findings of the previous funding period in rats and mice to human breast tumors to determine if microenvironments exist in human tumors similar to those discovered in rats and mice during the previous funding period and if they can be used as landmarks in correlation with biomarkers to predict outcome. Combining multiphoton defined landmarks and molecular pathology studies with biomarkers derived from the Invasion Signature of the previous funding period, the prognostic value of master genes will be determined for human breast cancer. In addition, we are interested in determining if an invasion signature exists in humans, that is similar to that in rats and mice, containing master genes that can be used as biomarkers to predict outcome in human patients.