摘 要 胰腺癌是实体肿瘤中恶性程度最高的肿瘤之一，具有发病隐匿、手术切除率低、局部侵袭性强、早期容易发生转移、术后易复发、总体预后极差等特点。淋巴转移是胰腺癌最主要的转移方式，也是胰腺癌患者的早期不良预后事件，同时也是胰腺癌术后独立不良预后因子。胰腺癌淋巴转移的发生并不是偶然或随机事件，而更像是由肿瘤细胞与其周围微环境共同精心策划的。越来越多的研究表明，肿瘤转移起始细胞（或肿瘤干细胞）与肿瘤微环境在胰腺癌淋巴转移中起着“唱双簧”的作用。然而，参与整个转移过程的细胞与分子机制复杂，尚未完全阐明。本文结合近年相关文献对胰腺癌淋巴转移的细胞分子机制进行讨论。

关键词 胰腺癌 淋巴转移 肿瘤干细胞 微环境 分子信号通路

中图分类号：R735.9 文献标识码：A 文章编号：1006-1533（2016）08-0003-05

Advance in the research of molecular mechanism of lymphatic metastasis in pancreatic cancer

XIAO Zhiwen， YU Xianjun

（Department of Pancreatic Surgery， Cancer Hospital affiliated to Fudan University， Department of Oncology， Shanghai Medical College of

Fudan University， Pancreatic Cancer Institute of Fudan University， Shanghai 200032， China）

ABSTRACT Pancreatic cancer is widely known as one of the most challenging human malignancies for its insidious symptoms， low rate of surgical resection， high risk of local invasion， metastasis and recurrence， and overall dismal prognosis. Lymphatic metastasis， above all， is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells and the microenvironments may act as a double-reed style in this crime. However， the exact mechanism on how they function synergistically for this dismal clinical course is intricate and remains largely elusive. Therefore， a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review， we summarize the latest advances in lymphatic metastasis in pancreatic cancer.

KEY WORDS pancreatic cancer； lymphatic metastasis； cancer stem cell； microenvironment； molecular pathway

胰腺癌仍是21世纪的“顽固堡垒”，中位生存期不足6个月，5年生存率始终徘徊于5%左右，发病率却逐年升高，近30年西方国家胰腺癌发病率上升7倍[1]。上海市胰腺癌最新发病统计数据显示，男性发病粗率由11.13/10万（2001年）上升至17.28/10万（2009年），女性由9.91/10万（2001年）上升至14.04/10万（2009年），患者中位生存期也仅提高11.2个月，5年生存率提高8.2%，形势极为严峻[2]。

胰腺癌具有很强的侵袭、转移和复发特性，其中淋巴转移十分常见[3-5]。许多胰腺癌患者即使获得R0切除，短时间内仍会出现淋巴转移而使治疗失败。胰腺癌淋巴转移的特征为：①发生早，小胰癌（≤2 cm）患者淋巴转移的发生率可达37.2%[6]；……