Exploration of new therapy and diagnosis in lymph metastasis of lung cancer based on theprofile of lymphangiogenic-related genes expression

基于我们对肿瘤微环境（TM）重要性的认识，TM诱导恶性表型的获得，如上皮-间质转化（EMT），导致转移到淋巴结。在本研究中，在活体原位肺内植入模型中，持续组织缺氧可能涉及肿瘤组织。持续缺氧也能诱导肺癌细胞中稳定的HIF1α表达。用强力霉素诱导的基因表达系统将HIF1α转导到肺癌中引起VEGF-A的新生表达。结合前哨淋巴结淋巴内皮细胞中VEGF受体表达增加的证据，缺氧可能是肺癌转移到淋巴结和淋巴管生成的治疗靶点。

Based on our recognition for the importance of tumor microenvironment(TM), TM induces acquisition of malignant phenotype such as epithelial-mesenchymal transition (EMT), resulting in metastasis into lymph nodes. In this study, persistent tissue hypoxia might be involved in tumor tissue in an in vivo orthotopic intrapulmonary implantation model. Persistent hypoxia also induced the stabilized HIF1α expression in lung cancer cells. Transduction of HIF1α into lung cancers with the Doxycycline inducible gene expression system caused de novo VEGF-A expression. Taken together with the evidence of increasing VEGF receptor expression lymphatic endothelial cells in sentinel lymph nodes, hypoxia as TM in lung cancers might be a therapeutic target for the metastasis into lymph nodes and lymphangiogenesis.