CACNA2D1靶向非小细胞肺癌肿瘤干细胞的作用机制及临床治疗意义的研究

Cancer stem cells (CSCs) within tumor have the properties of self-renewal, infinite proliferation and differentiation and play an important role in the development of tumor. The existing therapies eradicate the majority of tumor but not the CSCs, and these CSCs will cause recurrence and relapse. It has been found that CACNA2D1（α2δ1）highly aberrantly expressed in the recurrent liver tumor and targeted CSCs and had the potential to inhibit growth of liver cancer. Therefore, this project want to study α2δ1, as a specific surface marker for lung CSCs and the molecular mechanism. Meanwhile, α2δ1 is investigated in the lung cancer clinical samples and relationship between this marker expression and clinical characteristics are analyzed that can provide basis for evalution of recurrence, migration and prognosis.

肿瘤干细胞是肿瘤中具有自我更新、无限增殖和多向分化潜能的细胞，是恶性肿瘤发生、发展的关键。现有治疗肿瘤的方法主要是针对肿瘤组织内的大多数细胞，而不是肿瘤干细胞，只要有肿瘤干细胞存在，仍然会造成肿瘤的复发和转移。CACNA2D1（α2δ1）在肝癌复发转移肿瘤中异常高表达，具有靶向肿瘤干细胞，抑制肿瘤生长的潜能。因此，本项目拟围绕α2δ1作为肺癌肿瘤干细胞特异性表面标志物，深入研究α2δ1对于非小细胞肺癌细胞功能的影响及分子作用机制。同时利用标本资源，检测α2δ1在肺癌标本的表达状态，分析其与临床指标的相关性，为肺癌患者预后的判断提供事实依据。

肿瘤干细胞是肿瘤中具有自我更新、无限增殖和多向分化潜能的细胞，是恶性肿瘤发生、发展的关键。因此，本项目围绕CACNA2D1（α2δ1）作为肺癌肿瘤干细胞特异性表面标志物展开研究。本项目发现α2δ1+细胞亚群球体形成能力，干细胞相关因表达水平及致瘤性均明显高于α2δ1-，提示α2δ1是肺癌干细胞的分子标志物。同时，α2δ1的单克隆抗体1B50-1联合铂类可有效抑制小鼠肺移植肿瘤的生长。研究结果显示α2δ1高表达与非小细胞肺癌预后差相关。分子生物学实验结果显示α2δ1+细胞的干细胞特征与NOTCH1和NOTCH3的信号通路有关。综上所述，α2δ1可作为肺癌干细胞的标志物和潜在的治疗靶点。