胰腺癌TME中PSC通过IL22/IL22R/STAT3/SOSC3轴信号通路促进胰腺癌干细胞特性的分子机制研究

胰腺癌恶性度高，预后差。胰腺癌肿瘤微环境（TME）中胰腺星状细胞（PSC）在胰腺癌的恶性进展和化疗耐药方面起重要作用。已有研究报道PSC可通过促进胰腺癌干细胞特性影响胰腺癌恶性进展。细胞因子白介素22（IL22）不仅参与炎症和修复，而且参与多种恶性肿瘤的进展过程。我们前期研究已发现IL22及IL22R与胰腺癌预后不良相关，STAT3激活参与此过程。进一步发现高表达IL22的PSC可促进胰腺癌的侵袭转移。最新研究显示IL22RA1/STAT3信号通路可促进胰腺癌干细胞特性和恶性进展。因此IL22/IL22R/STAT3/SOCS3轴信号通路很可能在PSC促进胰腺癌干细胞特性这一过程中起关键作用。本课题拟从胰腺癌TME中PSC着手，从体内外水平深入阐明其通过IL22R/STAT3/SOCS3轴信号通路促进胰腺癌干细胞特性的分子机制，为胰腺癌的综合治疗提供新的靶点和策略。

Pancreatic cancer is one of the most aggressive cancers. Pancreatic stellate cells（PSC）in pancreatic tumor microenviroment (TME) play important role in tumorigenicity, chemotherapy resistance, recurrence and metastasis of pancreatic cancer. It has been reported that PSC can promote stemness of pancreatic cancer. Interleukin22 (IL-22) is a cytokine involved not only in inflammatory and healing processes, but also in progress of many malignant diseases. Our previous study found that high expression of IL-22 and IL-22R was associated with poor prognosis of pancreatic cancer by activating STAT3. Moreover, PSC of high expression IL-22 can promote invasion and progression of pancreatic cancer. The latest study showed that IL22RA1/STAT3 signal pathway can promote stemness of pancreatic cancer and result in malignant progression of pancreatic cancer. So we believe that IL22/IL22R/STAT3/SOCS3 axis signaling pathway might play a vital role in PSC promoting stemness of pancreatic cancer. But the target and mechanism is largly unclear. We will study the role mechanism of PSC promoting stemness of pancreatic cancer through IL22/IL22R/STAT3/SOCS3 axis signaling pathway from vitro and vivo experiment. It might provide target and new therapeutic strategy for pancreatic cancer.