Wu Hsiang-Ling, Chu You-Hsiang, Tai Ying-Hsuan, Tsou Mei-Yung, Wu Cheng-Hsien, Lo Wen-Liang, Tai Shyh-Kuan, Yeh Chun-Chang, Lu Chih-Cherng
Department of Anesthesiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-pai Rd, Taipei, 11217, Taiwan.
School of Medicine, National Yang-Ming University, Taipei, Taiwan.
World J Surg Oncol. 2020 Aug 16;18(1):209. doi: 10.1186/s12957-020-01991-9.
Angiopoietin-Tie2 and nitric oxide pathway is crucial in tumor angiogenesis and closely correlates with tumor development, growth, and metastasis. This study aimed to investigate the angiopoietin-Tie2 and nitric oxide signaling of the erythrocyte membrane in response to surgical trauma in head and neck cancer.
We prospectively enrolled the patients with histology-proven head and neck squamous cell carcinoma undergoing surgical resection of primary tumors at the medical center between August and November 2019. We measured the preoperative and postoperative levels of angiopoietin-1, angiopoietin-2 in plasma using enzyme-linked immunosorbent assays, nitric oxide in plasma using nitrate/nitrite colorimetric assays, and Tie2 phosphorylation in erythrocyte membrane using Western blotting.
The plasma angiopoietin-1 was downregulated from the median 971.3 pg/mL (interquartile range [IQR] 532.1-1569.3) to 417.9 (IQR 270.5-597.3) after tumor resection (p = 0.0020). Conversely, the plasma angiopoietin-2 was enhanced from 1173.6 pg/mL (IQR 977.7-1450.2) to 2353.7 (IQR 1352.4-2954.3) after surgery (p = 0.0021), with a concomitant increase in plasma nitric oxide level from 7.73 μM (IQR 5.39-10.06) to 10.50 (IQR 7.65-14.18) after surgical resection (p = 0.0093). Subgroup analyses further showed the angiopoietin-Tie2 and nitric oxide signaling was significant only in stage III and IV cancer.
The dynamic change of angiopoietin-Tie2 signaling in the erythrocyte membrane along with the enhanced nitric oxide in plasma after tumor resection suggests erythrocytes play a significant role in modulating surgery-induced angiogenesis, which may provide a novel marker for cancer surveillance and control.
血管生成素 - Tie2和一氧化氮途径在肿瘤血管生成中至关重要，且与肿瘤的发生、发展及转移密切相关。本研究旨在探讨头颈部癌手术创伤后红细胞膜上血管生成素 - Tie2和一氧化氮信号通路的变化。
我们前瞻性纳入了2019年8月至11月期间在该医疗中心接受原发性肿瘤手术切除且经组织学证实为头颈部鳞状细胞癌的患者。我们采用酶联免疫吸附测定法测量术前和术后血浆中血管生成素 - 1、血管生成素 - 2的水平，采用硝酸盐/亚硝酸盐比色法测量血浆中一氧化氮的水平，并采用蛋白质印迹法测量红细胞膜上Tie2的磷酸化水平。
肿瘤切除后，血浆血管生成素 - 1从中位数971.3 pg/mL（四分位间距[IQR] 532.1 - 1569.3）下调至417.9（IQR 270.5 - 597.3）（p = 0.0020）。相反，术后血浆血管生成素 - 2从1173.6 pg/mL（IQR 977.7 - 1450.2）升高至2353.7（IQR 1352.4 - 2954.3）（p = 0.0021），同时手术切除后血浆一氧化氮水平从7.73 μM（IQR 5.39 - 10.06）升高至10.50（IQR 7.65 - 14.18）（p = 0.0093）。亚组分析进一步显示，血管生成素 - Tie2和一氧化氮信号通路仅在III期和IV期癌症中具有显著变化。
肿瘤切除后红细胞膜上血管生成素 - Tie2信号通路的动态变化以及血浆中一氧化氮水平的升高表明，红细胞在调节手术诱导的血管生成中发挥着重要作用，这可能为癌症监测和控制提供一种新的标志物。
