非经典谷氨酰胺代谢是胰腺癌赖以生存、独特的生物学行为。炎症微环境是影响肿瘤恶性生物学行为的关键因素，研究表明肿瘤相关巨噬细胞（TAMs）可通过影响肿瘤能量代谢进而促其发展，我们前期已建立TAMs与胰腺癌细胞共培养体系，发现TAMs分泌CCL18促进胰腺癌非经典谷氨酰胺代谢，但具体机制尚不明确。进一步预实验：①基因芯片结果显示TAMs可上调胰腺癌细胞长非编码RNA LOC389641表达；②体外实验提示LOC389641联合c-Myc参与CCL18上调谷氨酰胺代谢关键酶GLS1表达过程。基于此，本项目提出“TAMs经CCL18/PITPNM3/LOC389641轴调控胰腺癌谷氨酰胺代谢重编程”的假说，通过代谢组学检测、RNA pull-down、免疫共沉淀、突变序列构建等方法阐明其分子机制，拟为靶向胰腺癌特异性代谢模式治疗提供新的思路，为后续开发“胰腺癌代谢+炎症微环境”双靶向药物奠定基础。

Pancreatic cancer relies on a non-canonical glutamine metabolism,which is a distinctive biological behavior.Inflammatory microenvironment plays a pivotal role in tumor progression and metastasis.Studies have shown that tumor-associated macrophages (TAMs) promote the progression of cancers via influencing their energy metabolism.In our previous research,by a coculture system of TAMs and pancreatic cancer cells,we found that TAMs promoted the non-canonical glutamine metabolism of pancreatic cancer through the paracrine secretion of CCL18.However,the concrete mechanism remains unknown.Further preliminary experiments showed that:1.TAMs upregulated the expression level of long non-coding RNA LOC389641 in pancreatic cancer cells by microarrays.2.By physically interacting with c-Myc,LOC389641 might be a co-activator in the process of upregulation of glutaminase GLS1 (a key enzyme in glutamine metabolism) caused by CCL18 in vitro.As mentioned above,we put forward the scientific hypothesis that TAMs regulate reprogramming of glutamine metabolism in pancreatic cancer via CCL18/PITPNM3/LOC389641 axis.Several important experimental methods including metabolomics,RNA pull-down,co-immunoprecipitation and construction of mutant sequence will be used to illuminate the exact molecular mechanism.We aim to provide new viewpoints for improvement of therapeutic approaches by targeting pancreatic cancer-specific metabolic phenotypes.Meanwhile,we will lay the foundation for the subsequent development of specific drugs targeting on both metabolism of pancreatic cancer and inflammatory microenvironment.