Lymphangiogeneis and Metastasis During Pancreatic Cancer Progression

胰腺癌进展过程中的淋巴管生成和转移

• 批准号: 8555505
• 负责人: Michael A. Hollingsworth
• 金额: $ 17.36万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-26 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8555505
• 关键词: Adenocarcinoma; Autopsy; Biological; Cancer Patient; Desmoplastic; Ductal Epithelial Cell; Environment; Erinaceidae; Freezing; Invaded; Lymphangiogenesis; Lymphatic; Lymphatic Endothelial Cells; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of pancreas; Metastatic Neoplasm to Lymph Nodes; Modeling; Molecular; Nature; Neoplasm Metastasis; Pancreas; Paracrine Communication; Pathway interactions; Premalignant; Primary Neoplasm; Process; Proteomics; Publishing; RNA Sequences; Reaction; Role; Sampling; Signal Pathway; Signaling Protein; Technology; Tissue Sample; Work; base; inhibitor/antagonist; laser capture microdissection; lymph nodes; neoplastic cell; pancreatic neoplasm; tissue resource; tumor; tumor progression

We propose to study lymphatic invasion and metastasis to lymph nodes, an early feature of metastasis of all adenocarcinomas. This proposal is to study the process of lymphatic invasion and metastasis in pancreatic cancer by undertaking both hypothesis-driven and hypothesis-generating specific aims. The first aim, which is hypothesis driven, seeks to further invesfigate the role of Sonic Hedgehog (SHH) in tumor lymphangiogenesis and metastasis to lymph nodes. SHH is expressed in premalignant and malignant ductal epithelial cells of the pancreas, implicafing this morphogenic signaling protein in the inifiafion and progression of pancreafic cancer. Aim 1 will build upon our recent published work [1] and other recent unpublished findings. We were the first to show that SHH contributes significantly to lymphangiogenesis by invesfigating the nature of paracrine signaling between pancreatic tumor cells producing SHH and lymphatic endothelial cells that are responding to SHH in the context of the emerging desmoplasfic reaction in pancreatic cancer.

我们建议研究淋巴管侵袭和淋巴结转移，这是淋巴癌的早期特征 所有腺癌的转移。本提案是研究淋巴管侵袭和转移的过程 通过实现假设驱动和假设生成的具体目标来治疗胰腺癌。 第一个目标是假设驱动的，旨在进一步研究 Sonic Hedgehog (SHH) 在 肿瘤淋巴管生成和淋巴结转移。 SHH在癌前和恶性中表达 胰腺导管上皮细胞，在起始和发生过程中涉及这种形态发生信号蛋白 胰腺癌的进展。目标 1 将建立在我们最近发表的工作 [1] 和其他最近发表的工作的基础上 未发表的发现。我们是第一个证明 SHH 对淋巴管生成有显着贡献的人 研究产生 SHH 的胰腺肿瘤细胞与淋巴管之间的旁分泌信号传导性质 在胰腺中出现的促纤维化反应背景下对 SHH 做出反应的内皮细胞 癌症。