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Cancer Res:手术促进结直肠癌肝转移的风险

手术是治疗结直肠癌的主要手段之一。匹兹堡大学的Allan Tsung发现,手术过程本身也可能会促使结直肠癌肝转移。
中性粒细胞是响应手术损伤的第一批免疫细胞。这些细胞会在血液中释放出富含蛋白的DNA,被称为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。
这项研究告诉我们,减少血液中的NET可以降低手术后结直肠癌复发的风险。
 
参阅文献:
 
Neutrophil Extracellular Traps Promote the Development and Progression of Liver Metastases after Surgical Stress
Cancer Res March 15, 2016 76; 1367
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. Cancer Res; 76(6); 1367–80. ©2016 AACR.
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