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

上皮-间充质转化(EMT)的重新激活被认为是癌症转移的潜在驱动力。接受EMT的癌细胞通常表现为细胞连接丢失和迁移能力增强。然而，不同的EMT激活剂通过不同的信号通路发挥作用。瑞典Solna的Jonas Fuxe教授的研究小组最近发现，稳定在自分泌转化生长因子-β1诱导的乳腺癌细胞(简称EMT细胞)具有明显更高的迁移到淋巴管和引流淋巴结的倾向，而不是迁移到血管中，这表明转化生长因子-β1诱导的EMT的存在可能对高淋巴结转移率的乳腺癌患者具有重要意义。然而，EMT细胞是否能够进一步迁移到体循环中，以及它们最终是否会在远处的器官中定植，仍有待研究。在这个项目中，双光子显微镜将与瑞士贝林佐纳的圣地亚哥·冈萨雷斯教授合作进行，以确定EMT细胞在进入引流淋巴结后如何迁移。此外，还将分析炭疽毒素受体2在转化生长因子-β1诱导的内胚层转移中的作用及其在乳腺癌中的潜在临床意义。该项目的目的是表征转化生长因子-β1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.