PNAS：铲除转移性癌症的新策略

    来自康奈尔大学的生物医学工程师们，发现了一种消灭转移性癌症的新方法：让杀癌蛋白质骑在白细胞上搭乘便车来破坏通过血流传播的转移癌细胞。

    研究的资深作者、康奈尔大学生物医学工程学教授Michael King说：“这些循环癌细胞劫数难逃。大约90%的癌症死亡都与转移相关，现在我们找到一种方法来调度杀伤性白细胞军队引起癌细胞凋亡，将它们清除出血流。当被这些家伙包围之时，癌细胞想要逃脱出去几乎是不可能的事情。” 
    转移是指癌细胞扩散至身体其他部位的一个过程。尽管手术和放疗能够有效地治疗原发性肿瘤，但难以检测到转移癌细胞使得治疗扩散性癌症成为了一个难题。
    King和同事们将两种蛋白：E-selectin和TRAIL添加到人类血液样本中，随后将其注入到小鼠体内。TRAIL结合E-selectin能够附着到血流中含量丰富的白细胞上。当癌细胞在血液流动中不可避免地接触到TRAIL之时，癌细胞就会自发地杀死自己。
    “并非采用脂质体或可溶性蛋白来直接靶向癌细胞，而是将目标调整为流动血液中的白细胞，这一机制令人惊讶且出乎意料之外，”作者们说。
在实验室，King和同事们测试了这一想法的效力。
    当他们将蛋白质放置到生理盐水中来处理癌细胞时，发现癌细胞杀伤成功率达到60%。在普通实验室条件下，生理盐水中缺乏充当粘附性或杀伤性蛋白质载体的白细胞。而当将这些细胞添加到流动血液中模拟人体状况时，研究人员发现癌细胞杀伤率跃升至了接近100%。
    这一研究成果发表在《美国科学院院刊》（PNAS）杂志上。


推荐原文索引： 
“RAIL-Coated Leukocytes that Kill Cancer Cells in the Circulation,"  Proceedings of the National Academy of Sciences.

摘要：
TRAIL-coated leukocytes that kill cancer cells in the circulation

Michael J. Mitchell, Elizabeth Wayne, Kuldeepsinh Rana, Chris B. Schaffer, and Michael R. King

Metastasis through the bloodstream contributes to poor prognosis in many types of cancer. Mounting evidence implicates selectin-based adhesive interactions between cancer cells and the blood vessel wall as facilitating this process, in a manner similar to leukocyte trafficking during inflammation. Here, we describe a unique approach to target and kill colon and prostate cancer cells in the blood that causes circulating leukocytes to present the cancer-specific TNF-related apoptosis inducing ligand (TRAIL) on their surface along with E-selectin adhesion receptor. This approach, demonstrated in vitro with human blood and also in mice, mimics the cytotoxic activity of natural killer cells and increases the surface area available for delivery of the receptor-mediated signal. The resulting “unnatural killer cells” hold promise as an effective means to neutralize circulating tumor cells that enter blood with the potential to form new metastases.