PROJECT 4:MECHANISMS FACILITATING GROWTH & METASTASIS OF PANCREATIC CANCER

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 胰腺癌是美国与癌症相关的死亡的第四大常见原因，也是 大约5%的患有这种疾病的患者存活下来。提高了对胰腺肿瘤如何生长和发展的理解 为了开发更好的治疗方法，转移是必要的。在某些系统中，主要是 神经系统、淀粉样前体蛋白(APP)和淀粉样前体蛋白2(APLP2) 与细胞生长和迁移有关。最近的研究表明APP和APP的过度表达 APLP2在人类癌症中，包括胰腺癌，以及在一些癌症中表达较高 显示出与较差的存活率相关。前列腺癌和胰腺癌细胞株分泌的APP 通过与一种未知的细胞表面受体结合促进增殖，APP和APLP2 有助于多种细胞类型的粘附性和运动性。有证据表明，APP和APLP2具有新颖的 在胰腺癌中的作用，但它们如何导致这种疾病的机制尚不清楚。在这 项目中，我们的总体目标是了解胰腺癌生长的机制。 并蔓延开来。我们的中心假设是APP和APLP2刺激肿瘤的增殖和转移 胰腺癌细胞。为了实现这一目标，我们的目标是，首先确定中介机制 通过APP和APLP2促进胰腺癌细胞的生长。我们对这一目标的工作假设是 分泌的APLP2和APP通过核因子-B途径激活胰腺癌细胞的增殖。这个 第二个目标是确定APP和APLP2介导的增加病毒传播的机制 胰腺癌细胞。将在这一目标中检验的工作假设是跨膜APP 和APLP2是胰腺癌细胞黏附和扩散的关键调节因子。我们的结果 这些研究将为调节细胞生长和运动提供一个新的视角， 与正常细胞和癌细胞，特别是与胰腺癌细胞的相关性。此外，结果来自 这项研究有望支持针对APP和APP的胰腺癌新疗法的使用。 APLP2.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Pancreatic cancer is the fourth most frequent cause of cancer-related death in the U.S., and only about 5% of patients with this disease survive. Improved comprehension of how pancreatic tumors grow and metastasize is necessary in order for better therapies to be developed. In some systems, principally the nervous system, amyloid precursor protein (APP) and amyloid precursor-like-protein 2 (APLP2) have been associated with cellular growth and migration. Recent studies have shown over-expression of APP and APLP2 in human cancer, including pancreatic cancer, and in some cancers higher APP expression has been shown to correlate with a worse survival rate. APP secreted by prostate and pancreatic cancer cell lines increases proliferation by binding to an unidentified cell surface receptor, and both APP and APLP2 contribute to adhesion and motility in several cell types. There is evidence that APP and APLP2 have novel roles in pancreatic cancer, but the mechanisms for how they contribute to this disease are not known. In this project, our overall objective is to gain understanding of mechanisms underlying pancreatic cancer growth and spread. Our central hypothesis is that APP and APLP2 stimulate the proliferation and metastasis of pancreatic cancer cells. To accomplish this objective, our Aims are, first, to ascertain mechanisms mediated by APP and APLP2 that facilitate pancreatic cancer cell growth. Our working hypothesis for this aim is that secreted APLP2 and APP trigger the proliferation of pancreatic cancer cells via a NF-¿B pathway. The second aim is to determine mechanisms mediated by APP and APLP2 that increase the spread of pancreatic cancer cells. The working hypothesis that will be tested in this aim is that transmembrane APP and APLP2 are key regulators of the adhesion and dissemination of pancreatic cancer cells. Our results from these studies will provide a novel perspective on the regulation of cellular growth and motility, with relevance to normal and cancer cells and particularly to pancreatic cancer cells. Furthermore, results from this study are expected to support the use of novel treatments for pancreatic cancer that target APP and APLP2.