外泌体参与调控胰腺癌细胞与脂肪细胞等间质细胞对话，促进胰腺癌转移，但机制不明。本课题组前期研究发现：① linc-ROR可激活HIF-1α/ZEB1通路，促进胰腺癌转移；②胰腺癌细胞分泌的外泌体中linc-ROR高表达，与脂肪细胞共培养后IL-1β水平升高，增强胰腺癌细胞侵袭能力。基于此，我们提出如下假说：胰腺癌细胞来源外泌体linc-ROR进入脂肪细胞后上调HIF-1α活性，刺激脂肪细胞分泌IL-1β，后者可上调胰腺癌细胞HIF-1α和linc-ROR表达，形成正反馈环路，介导胰腺癌EMT，进而促进胰腺癌侵袭转移。本课题将临床标本检测和体内外实验相结合，采用体外细胞共培养、裸鼠体内成瘤等多种实验方法，从临床标本、细胞及动物等不同层面，探索胰腺癌细胞来源外泌体linc-ROR参与胰腺癌细胞-脂肪细胞对话，调控脂肪细胞去分化，促进胰腺癌侵袭转移的机制，为研究胰腺癌转移机制及临床诊治提供思路。

Exosome plays a pivotal role in modulation of crosstalk between cancer cells and stromal cells, including adipocytes in pancreatic cancer (PC), which further promotes the invasion and metastasis of PC, but the molecular mechanism still remains unclear.Our previous study confirmed that linc-ROR promoted cell proliferation, invasion and metastasis via HIF-1α/ZEB1 pathway in PC, level of tumor-secreted exosomal linc-ROR was elevated in PC cells and resulted in higher expression of IL-1β and promoted the invasion of PC after co-culture with adipocytes, but the molecular mechanisms should be further investigated. Based on the literature review and our previous study, we hypothesize that tumor-secreted linc-ROR could be incorporated into exosomes and transmitted to adipocytes, they can activate the HIF-1α pathway, promote adipocytes to secrete IL-1β, IL-1β can further promote expreesion of HIF-1α and linc-ROR in PC cells, induce the epithelial-mesenchymal transition (EMT), form a positive feedback loop between cancer cells and adipocytes, and finally enhance the invasion and metastasis of PC. To test the hypothesis, we will investigate role and mechanism of exosome-transmitted linc-ROR in regulation of crosstalk between PC cells and adopocytes, dedifferentiation of adipocytes, EMT process and invasion and metastasis in PC, the combination analysis of expression level of linc-ROR in serum exosome extracted from patients with PC, in vitro cell co-culture and in vivo tumor growth will be applied in the research. Our study will provide the new insights for understanding mechanism of PC metastasis and also lead to identify a new molecular target for early detection and targeted therapy in patients with PC.