TGF-beta信号通路在小细胞肺癌转移中的分子机制研究

Small cell lung carcinoma (SCLC) is the most aggressive lung cancer subtype, which is easy to metastasize, 90% of the patients died of metastasis. There is no functional and mechanisitic study of TGF-beta in SCLC metastasis, though it plays important role in the development of many cancer types. Animal model is the most useful tool for SCLC study, because only a few samples can be collected for surgery rarely used clinically. In order to study the mechanism of TGF-beta signaling pathway during SCLC metastasis, de novo mice models will be used to study the function and mechanism of TGF-beta signaling in SCLC metastasis. TGF-beta signaling pathway will be destroyed in the mice models Tgfbr2L/L and Smad4L/L. And the function of TGF-beta signaling in SCLC will be studied by crossing Rb1L/L, Trp53L/L with Tgfbr2L/L/Smad4L/L. The tumorigeneis and metastasis of these two models will be comparied with mouse SCLC model Rb1L/L, Trp53L/L, and the function of the TGF-beta signaling pathway in SCLC metastasis will be analyzed. More in vivo and in vitro experiments will be proposed to find the mechanism of TGF-beta signaling in SCLC metastasis. Hope these studies will provide us with novel strategies and theoretic basis for lung cancer early diagnosis and treatment in the near future.

小细胞肺癌（small cell lung carcinoma，SCLC）是一种恶性程度极高、生长迅速、容易侵袭和转移的肺癌类型，90%以上的患者死于肿瘤转移。众所周知，TGF-beta信号通路在多种癌症进展中发挥重要作用，但目前还没有其在SCLC转移中功能及机制研究。由于临床上SCLC患者极少手术治疗，能获得的肿瘤样本极少，动物模型便成为SCLC研究的最佳手段。本课题将利用条件敲除小鼠模型 Tgfbr2L/L和Smad4L/L抑制TGF-beta信号通路的活性，通过与Rb1L/L, Trp53L/L杂交获得Rb1L/L， Trp53L/L，Tgfbr2L/L和Rb1L/L，Trp53L/L，Smad4L/L条件敲除小鼠，研究TGF-beta信号通路在SCLC转移中的作用，阐明该信号通路在SCLC转移中发挥作用的分子机制，为SCLC的临床治疗提供理论依据和新的思路。