Analyses of influence by Warburg Effect small molecular Metbolites via Cancer-Stroma interactions

肿瘤组织内部及周围经常出现局部小分子代谢产物浓度波动，如因Warburg效应产生的乳酸或丙酮酸。在本研究计划中，我们将通过肿瘤-基质相互作用，研究这些代谢物浓度变化对肿瘤组织、维持和恶化的分子影响和独特表达机制。利用肿瘤细胞和间质细胞共培养的细胞模型系统，利用新型生物信息学技术，从集成的DNA芯片表达数据中，成功地读取了各细胞组的半独立表达谱。提取了几个基因产物，并证实这些表达对代谢物浓度变化有特异性反应。分子信号转导途径是通过实验推测的，使用具有小分子代谢物、抑制剂和激活剂的类似分子结构的试剂进行Warburg效应。

Local fluctuations of small molecular metabolic products concentration, like lactate or pyruvate produced with Warburg effect, were frequently seen in and around cancer tissue. In this research plan, we investigate molecular influences and mechanism of unique expression due to these metabolites concentration changes, via cancer - stroma interaction, for organization, maintenance, and exacerbation of cancer.Using co-cultured cell model system composed with cancer cell and stroma cell, we successfully perused semi-independent expression profiles of each cell group from integrated DNA chip expression data with novel bio-informatics techniques. Several gene products were extracted, and certified as these expressions were specifically responded to those metabolite concentration changes. Molecular signal transduction pathways were presumed by experiments using reagents showing resembled molecular - structure with small molecular metabolites, inhibitors, and activators for Warburg effect.