特络细胞在食管癌中的作用和分子机制研究

The interaction between stromal cells and tumor cells, is an important factor affecting the development of tumors. The telocytes as of a kind of newly discovered interstitial cell, its structure and function have all shown its important role in the exchange of signals between cells. Our previous studies isolated and identified telocytes from both esophageal normal and paraneoplastic tissue. Although the gene expression , features , and the difference of telocytes in between esophageal normal and paraneoplastic tissue were not clear, our initial findings revealed that, telocytes secrete a variety of angiogenic factors, so we thought it promoted cancer's growth especially angiogenic process. Our previous study found that telocytes in paraneoplastic tissue secreted more angiogenic factors than their partners in normal esophageal tissue, and they grew faster, this difference might be caused by the interaction between telocytes and cancer cells. We will detect the genome expression of telocytes in human esophageal normal and paraneoplastic tissue, to clarify their features , molecular mechanisms and differences. Then we will detect the changes of their genome expression and features when telocytes are co-cultured with cancer cells, make clear their interactions and mechanisms. Meanwhile, we eill test the specific role of telocytes in cancer angiogenesis through cell and animal experiments. Our research will provide a new pathway for the targeted therapy of esophageal cancer.

间质细胞与肿瘤细胞间的相互作用，是影响肿瘤发生发展的重要因素。而特络细胞作为一种新发现的间质细胞，其结构和功能都显示出它在细胞间信号交流中的重要地位。我们前期研究从食管正常和癌旁组织中分别分离鉴定了特络细胞。虽然目前正常和癌旁食管特络细胞的基因表达、功能特点以及二者差异尚不明确，但我们初步研究发现，食管特络细胞高分泌多种血管生成因子，因此我们认为其可能参与食管癌发生发展特别是血管生成进程。另外我们发现癌旁比正常食管特络细胞增殖和分泌能力更强，这种差异可能由特络细胞和癌细胞的相互作用所引起。本研究中我们将分别检测人食管正常和癌旁特络细胞的基因表达，研究二者各自的功能特点、分子机制以及差异。随后我们将检测人食管特络细胞和癌细胞共同培养时二者基因表达和功能特点的变化，明确它们的相互作用和机制。同时本课题将通过细胞和动物实验，检测特络细胞对食管癌血管生成的具体作用，为食管癌的靶向治疗提供新的思路。

课题组反复尝试对正常食管组织和食管鳞癌中的特络细胞进行分离，但因为特络细胞缺乏特定的细胞表面标记、分选的数量极少并且无法保证全部为特络细胞、细胞无法增殖等原因导致细胞数量不够，难以进行高通量测序因而项目无法进行。在本项目的资助下，我们对于食管鳞癌和正常食管组织基因和miRNA的差异表达及生物学功能、信号通路等进行了充分研究，并构建了食管鳞癌的转录因子——差异miRNA——差异基因的调控网络图。同时我们还鉴定了多个食管鳞癌和正常食管组织中的表达稳定的基因和mRNA，比较了这些基因和miRNA在应用于qRT-PCR中作为内参的价值并与传统的内参基因、内参miRNA进行了对比。另外，我们还充分研究了异时性第二原发肺癌的临床特点及治疗手段对预后的影响，以及肿瘤中PKM1和PKM2表达特点的变化等。