PDGF-BB和乳酸介导口腔鳞癌细胞与癌相关成纤维细胞糖代谢共生及机制研究

肿瘤演进过程中，癌细胞与基质细胞的代谢互作备受关注。癌相关成纤维细胞是肿瘤基质的主要组分，肿瘤进程对其高度依赖并与糖代谢密切相关，但机制未明。我们前期发现口腔鳞癌细胞能通过分泌血小板衍生生长因子-BB（PDGF-BB）将成纤维细胞糖代谢模式从氧化磷酸化切换为有氧糖酵，生成高能量代谢产物乳酸，反哺癌细胞。本项目拟通过建立口腔鳞癌细胞与成纤维细胞共培养模型，探索PDGF-BB和乳酸介导两细胞间的代谢偶联作用、信号转导途径及关键节点；建立裸鼠共移植模型体内分析癌细胞和成纤维细胞的代谢互作关系；行口腔鳞癌临床组织标本内相关因子表达或磷酸化水平检测进行验证。明确PDGF-BB和乳酸介导口腔鳞癌细胞与癌相关成纤维细胞糖代谢偶联共生作用及调节因子，从代谢互作角度阐明肿瘤演进机理并诠释癌细胞与成纤维细胞的内在关系及其分子事件，为探索通过干预PDGF-BB和/或乳酸作用逆转肿瘤发生发展奠定基础。

During tumour progression, the metabolic interaction between tumour cells and stromal cells has attracted much attention. Cancer-associated fibroblasts are the main components of stromal cells in the tumour microenvironments. Tumour progression is highly dependent on cancer-associated fibroblasts and is closely related to glycometabolism, but the mechanism is still unclear. Our previous study found that oral squamous cell carcinoma cells can induce glycometabolic reprograming in fibroblasts through secretion of platelet-derived growth factor-BB (PDGF-BB) and fibroblasts can feed cancer cells through lactate. In this study, a co-culture model of oral squamous cell carcinoma cells and cancer-associated fibroblasts will be established. The mechanism of PDGF-BB and lactate-mediated metabolic coupling between cancer cells and fibroblasts will be explored. The metabolic reprograming coupling between oral squamous cell carcinoma cells and cancer-associated fibroblasts will be explored in vivo through establishing a nude mouse co-transplantation model. Expressions of related factors and their phosphorylation will be detected in clinical specimens of oral squamous cell carcinomas. The research will clarify PDGF-BB and lactate-mediated glycometabolic symbiosis and regulatory factors between oral squamous cell carcinoma cells and cancer-associated fibroblasts, clarify the mechanism of tumor evolution from the perspective of metabolic interaction, and explain the intrinsic relationship between cancer cells and matrix fibroblasts and their molecular events. This study may lay the foundation for reversing the development of tumorigenesis by interfering PDGF-BB and/or lactate.