Influence of transforming growth factor-b1-induced epithelial-mesenchymal transition on breast cancer cell metastasis through lymphatic system

上皮-间质转化（EMT）的再激活被认为是癌症转移的潜在驱动力。经历EMT的癌细胞通常显示细胞连接的丧失和增强的迁移能力。然而，不同的EMT激活剂通过不同的信号通路起作用。Jonas Fuxe教授的研究小组（Solna，Sweden）最近证明，稳定地处于自分泌TGF-β 1诱导的EMT中的遗传改变的乳腺癌细胞，（缩写为EMT细胞）显示出明显更高的迁移到淋巴管和引流淋巴结中的倾向，但不迁移到血管中，提示TGF-b1诱导的EMT的存在可能特别在具有高淋巴结转移率的乳腺癌患者中具有重要意义。然而，EMT细胞是否能够进一步迁移到体循环中，以及它们是否最终在远处器官中定植，仍需要研究。在本项目中，将与圣地亚哥冈萨雷斯教授（贝林佐纳，瑞士）合作进行双光子显微镜检查，以确定EMT细胞进入引流淋巴结后如何迁移。此外，炭疽毒素受体2参与TGF-β 1诱导的EMT及其在乳腺癌中的潜在临床意义将进行分析。该项目的目的是描述TGF-b1诱导的EMT在具有高淋巴结转移率的乳腺癌患者中可能被低估的作用，并确定进一步的潜在治疗靶点。

Reactivation of epithelial-mesenchymal transition (EMT) is identified as a potential driving force for cancer metastasis. Cancer cells undergoing EMT generally show loss of cellular junction and enhanced migratory ability. However, different EMT activators operate through different signaling pathways. The research group of Prof. Jonas Fuxe (Solna, Sweden) recently demonstrated that genetically altered breast cancer cells which are stably in autocrine TGF-b1-induced EMT (abbreviated as EMT cells) show markedly higher tendency to migrate into lymphatic vessels and to draining lymph nodes, but not into blood vessels, indicating that presence of TGF-b1-induced EMT might have a major importance specifically in breast cancer patients with high rate of lymph node metastasis. However, whether EMT cells are in the position to migrate further into systemic circulation and whether they finally colonize in distant organs still need to be studied. In this project, two-photon microscopy will be conducted in collaboration with Prof. Santiago Gonzalez (Bellinzona, Switzerland) to determine how EMT cells migrate after entering draining lymph nodes. Furthermore, involvement of anthrax toxin receptor 2 in TGF-b1-induced EMT and its potential clinical significance in breast cancer will be analyzed. The purpose of the project is to characterize the possibly underestimated role of TGF-b1-induced EMT in breast cancer patients with high rate of lymph node metastasis and to identify further potential therapeutic targets.