Cancer Research惊人发现:手术本身推动癌症复发?
生物通/叶予 · 2016/04/12
结直肠癌又称大肠癌,是最常见的胃肠道恶性肿瘤之一。当结直肠癌转移到肝脏的时候,医生们通常会通过手术将肿瘤切除。然而,在大多数情况下癌症都是阴魂不散的。匹兹堡大学的Allan Tsung认为,手术过程本身(尤其是机体对手术损伤的修复应答)会促使癌症复发。


结直肠癌又称大肠癌,是最常见的胃肠道恶性肿瘤之一。当结直肠癌转移到肝脏的时候,医生们通常会通过手术将肿瘤切除。然而,在大多数情况下癌症都是阴魂不散的。匹兹堡大学的Allan Tsung认为,手术过程本身(尤其是机体对手术损伤的修复应答)会促使癌症复发。

中性粒细胞是响应手术损伤的第一批免疫细胞。这些细胞会向血液中喷出网状DNA,也就是中性粒细胞胞外诱捕网(NET)。越来越多的证据表明,NET不仅可以捕获致病菌,在癌症和其他疾病中也起到了重要作用。

Tsung及其同事发现,在肿瘤切除手术之后患者的血液含有NET,而且NET丰度越大肿瘤复发的风险就越高。用DNase处理小鼠可以降低NET水平和减少癌转移。麦吉尔大学的Lorenzo Ferri指出,循环肿瘤细胞可能被NET捕获和激活,生存和转移能力由此得到增强。

几个世纪以来一直有人相信,在肿瘤恶化之前不应轻易打搅它。“这种言论被许多人视为无稽之谈,但它可能有一定的正确性,”Tsung说。目前手术仍是治疗转移性结直肠癌的最佳选择,因此Tsung希望能够找到一种治疗方法,在不干扰中性粒细胞功能的同时限制其NET。

在许多癌症中,癌细胞的扩散才是最致命的威胁。人们往往可以通过手术、药物、化疗或者放疗成功治疗原发瘤,然而一旦癌症扩散到机体的其他器官就很难再进行遏制。已知上皮肿瘤的转移扩散依赖于一个胚胎发育程序的激活,即上皮-间充质细胞转化(EMT)。肿瘤细胞在这一过程中丧失自己的极性和细胞粘附,转变成了迁移和侵袭能力较强的间充质细胞。普林斯顿大学的康毅滨(Yibin Kang)教授最近在Cell旗下的trends in cancer杂志上发表了题为“Probing the Fifty Shades of EMT in Metastasis”的综述文章。文章介绍了癌转移领域EMT研究的一些最新进展,全方位探讨了EMT在癌转移中的多样性。

乳腺癌很容易扩散到骨骼、肺部、肝脏、淋巴结和大脑。抗癌药物对早期癌症的治疗效果最好,因此早期检测技术是非常关键的。目前用于乳腺癌检测的成像技术(包括MRI)既不能反映癌症类型,也无法检测出早期的癌细胞生长。凯斯西储大学的研究人员开发了一种磁共振成像(MRI)技术,可以检测到乳腺癌复发初期的生物学指标,这一研究成果发表在Nature Communications杂志上。

科学家们一直在尝试通过杀死肿瘤细胞来治疗癌症。而Johns Hopkins大学的研究团队提出了一种另类的抗癌策略:通过增强癌细胞的硬度,阻止它们扩散到机体其他部分。他们通过筛选找到了具有这种作用的化合物,并且测试了该化合物对胰腺癌的治疗潜力。这一成果发表在本周的美国国家科学院院刊PNAS杂志上。

所有文章仅代表作者观点,不代表本站立场。如若转载请联系原作者。
查看更多
  • Neutrophil Extracellular Traps Promote the Development and Progression of Liver Metastases after Surgical Stress

    Risks of tumor recurrence after surgical resection have been known for decades, but the mechanisms underlying treatment failures remain poorly understood. Neutrophils, first-line responders after surgical stress, may play an important role in linking inflammation to cancer progression. In response to stress, neutrophils can expel their protein-studded chromatin to form local snares known as neutrophil extracellular traps (NET). In this study, we asked whether, as a result of its ability to ensnare moving cells, NET formation might promote metastasis after surgical stress. Consistent with this hypothesis, in a cohort of patients undergoing attempted curative liver resection for metastatic colorectal cancer, we observed that increased postoperative NET formation was associated with a >4-fold reduction in disease-free survival. In like manner, in a murine model of surgical stress employing liver ischemia-reperfusion, we observed an increase in NET formation that correlated with an accelerated development and progression of metastatic disease. These effects were abrogated by inhibiting NET formation in mice through either local treatment with DNAse or inhibition of the enzyme peptidylarginine deaminase, which is essential for NET formation. In growing metastatic tumors, we found that intratumoral hypoxia accentuated NET formation. Mechanistic investigations in vitro indicated that mouse neutrophil–derived NET triggered HMGB1 release and activated TLR9-dependent pathways in cancer cells to promote their adhesion, proliferation, migration, and invasion. Taken together, our findings implicate NET in the development of liver metastases after surgical stress, suggesting that their elimination may reduce risks of tumor relapse.

    展开 收起
发表评论 我在frontend\modules\comment\widgets\views\文件夹下面 test