The role of chemokine/chemokine receptor systems in tumor progression of pancreatic ductal carcinoma

肿瘤细胞侵入淋巴管的机制尚不清楚。根据我们以前的研究和初步结果，我们假设胰腺癌是最具侵袭性的恶性肿瘤之一，它的淋巴结转移率很高，而没有功能相关的淋巴管生成，它可能利用了一种调节机制，控制着白细胞从器官到淋巴结的命运和通过淋巴管到达淋巴结的路径。这一过程是由在淋巴管中表达的趋化因子介导的，这些趋化因子吸引和引导趋化因子受体承载细胞。我们的主要目标是(1)明确胰腺癌中表达的趋化因子受体对淋巴管侵袭和淋巴结转移的意义；(2)确定淋巴管内皮细胞的基本趋化因子表达及其与胰腺癌细胞相互作用的调节方式；(3)明确瘤周慢性炎症引起的淋巴管趋化因子表达的变化及其对胰腺癌转移能力的影响。

The mechanism by which tumor cells invade lymphatic vessels is unknown. Based on our previous studies and preliminary results we hypothesize that pancreatic adenocarcinoma, which represents one of the most aggressive malignancies and shows a high rate of lymph node metastasis without functionally relevant lymphangiogenesis, may exploit a regulatory mechanism that controls the fate and route of white blood cells from organs to lymph nodes via lymphatic vessels. This process is mediated by chemokines which are expressed in lymphatics, attracting and directing chemokine receptor bearing cells. Our main goal is (i) to define the significance of chemokine receptors expressed in pancreatic adenocarcinoma for invasion into lymph vessels and for metastasis to lymph nodes (ii) to define the basal chemokine expression of lymphatic endothelial cells and how it is modulated by interaction with pancreatic adenocarcinoma cells, (iii) to define the alterations in the chemokine expression in lymph vessels due to peritumoral chronic inflammation and its effect on the metastatic capacity of pancreatic carcinomas.