Lymphangiogeneis and Metastasis During Pancreatic Cancer Progression

我们建议研究淋巴侵袭和淋巴结转移，这是淋巴转移的早期特征。 所有腺癌的转移情况。本研究旨在研究淋巴侵袭转移的过程。 在胰腺癌中，通过承担假设驱动和假设生成的特定目标。 第一个目标是假设驱动的，寻求进一步研究Sonic Hedgehog(SHH)在 肿瘤淋巴管生成与淋巴结转移。Shh在癌前病变和癌前病变中的表达 胰腺导管上皮细胞，涉及这种形态发生的信号蛋白在胰腺和 胰腺癌的进展。目标1将建立在我们最近发表的工作[1]和其他最近的 未发表的发现。我们是第一个证明SHH通过以下途径显著促进淋巴管生成的人 分泌SHH的胰腺肿瘤细胞与淋巴管旁分泌信号性质的研究 胰腺中新出现的结缔组织增殖性反应中对SHH有反应的内皮细胞 癌症。

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 Aim 1 will build upon our recent published work [1] and other recent unpublished findings.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.