化疗耐药是肺腺癌临床治疗面临的重大难题。既往研究大多集中在肿瘤细胞自身，近年来肿瘤微环境在肿瘤耐药中的作用受到越来越多的关注。课题组前期研究发现化疗后肿瘤相关成纤维细胞（CAF）能分泌IL-11促进肺腺癌顺铂耐药，且组织中CAF的比例与化疗耐药关系密切。但肿瘤细胞招募CAF的具体机制仍不清楚。研究表明，趋化因子在肿瘤细胞招募间质细胞中起着重要作用。课题组前期证实CCL28是乏氧状态下肺腺癌细胞唯一表达上调的趋化因子；Western Blot证实CAF表达CCL28受体CCR10；Transwell试验证实CCL28可以促进CAF的迁移。本项目旨在探讨肺腺癌细胞上调表达CCL28，并结合CAF的CCR10受体，调控CAF迁移至肿瘤间质，并通过IL-11/IL-11R/STAT3通路促进肺腺癌细胞耐药。本研究加深肿瘤微环境对肿瘤细胞化疗耐药机制的认识，为逆转肺腺癌化疗耐药提供新的靶点和方向。

Chemoresistance represents the major obstacle in clinical treatment of lung adenocarcinoma. Most of previous studies have focused directly on cancer cells, tumor microenvironment in facilitating chemoresistance is getting more and more attention. Our previous results have demonstrated that cancer associated fibroblast (CAF) could promote lung adenocarcinoma resistance to cisplatin through IL-11, and the ratio of CAF in tumor tissue plays a vital role in chemoresistance. However, the mechanism of fibroblasts recruited by cancer cells is still unclear. The studies have proved that chemokine plays an important role in recruiting stromal cells. Based on our previous studies on the gene expression array of lung adenocarcinoma cells under hypoxia condition, and confirmed by in vitro and in vivo research, CCL28 is the only up-expressed chemokine of lung adenocarcinoma cells in hypoxia. CCR10, as the receptor of CCL28, which expressed in CAF was verified by Western Blot. The result of Transwell experiment demonstrated that CCL28 could promote the migration of CAF. In the basis of previous results, this project investigates via in vitro and in vivo models that CCL28 which is upregulated by cancer cells in hypoxia could promote migration of CAF into tumor stroma through binding its receptor CCR10, ultimately contributing to the chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway. This research is helpful for a deeper understanding of the interaction between tumor cells and tumor microenvironment in the formation of chemoresistance, and providing new insight and target for reversing chemoresistance of lung adenocarcinoma.