Evaluation of metastatic niches in distant organs after surgical removal of tumor-bearing lymph nodes.
Evaluation of metastatic niches in distant organs after surgical removal of tumor-bearing lymph nodes.
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DOI：
10.1186/s12885-018-4538-8
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发表时间：
2018-05-30
期刊：
影响因子：
3.8
通讯作者：
Kodama T
中科院分区：
文献类型：
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作者：
Zheng J;Jia L;Mori S;Kodama T
手术切除原发肿瘤可促进肿瘤转移的发生。然而，这一过程背后的分子机制仍不清楚。我们将表达荧光素酶基因的肿瘤细胞接种到 MXH10/Mo-lpr/lpr 小鼠的髂淋巴结 (SiLN) 中。接种后一定时间通过手术切除携带肿瘤的 SiLN。体内生物发光成像系统和组织学染色显示肺、腋窝淋巴结（PALN）和肝脏的转移。根据Fisher精确检验，SiLN去除组的肺转移率显着高于对照组。 Mann-Whitney U检验表明，肺和肝中荧光素酶阳性肿瘤细胞明显高于对照组。 SiLN去除组的肺样本具有强烈的赖氨酸氧化酶（LOX）表达。此外，SiLN去除组肺和肝中CD11b+细胞数量显着增加，与LOX表达水平呈正相关。此外，肝脏中LOX和CD11b的情况与肺相似。 SiLN手术切除组肺组织中基质金属蛋白酶（MMP）-2和VEGFA表达量显着高于对照组；根据 Spearman 的分析，肺血管周围单位面积的胶原纤维显着降低，并且与 MMP-2 的表达呈负相关。我们的数据表明，切除组的肺部肿瘤组织中网状纤维沉积且紊乱，并且单位面积的网状纤维高于对照组。对照组PALN中肿瘤细胞明显高于SiLN去除组，CD169+和CD11c+细胞也高于SiLN去除组。总而言之，手术切除荷瘤淋巴结通过改变肺和肝脏中的生态位促进了肿瘤转移。针对转移生态位的治疗可能是预防肿瘤转移的有效策略，从而可能提高癌症患者的生存率并降低转移的发生率。
Surgical removal of primary tumors can promote the incidence of tumor metastasis. However, molecular mechanisms underlying this process remain unclear. We inoculated tumor cells expressing luciferase gene into subiliac lymph node (SiLN) of the MXH10/Mo-lpr/lpr mice. The tumor-bearing SiLNs were surgically removed at a certain period of time after inoculation. In vivo bioluminescence imaging system and histological staining revealed metastasis in lung, proper axillary lymph node (PALN) and liver. The lung metastasis rate in SiLN removal groups was significantly higher than in the control group using Fisher exact test. Mann-Whitney U-test indicated that the luciferase-positive tumor cells in the lung and liver were significantly higher than in the control groups. The lung samples in SiLN removal groups had strong expression of lysine oxidase (LOX). Moreover, the number of CD11b+ cells in the lung and liver in the SiLN removal groups was significantly increased, which was positively correlated with LOX expression level. In addition, the condition of LOX and CD11b in liver was similar to lung. In the SiLN surgical removal groups, the matrix metalloproteinase (MMP)-2 and VEGFA expression in the lung tissues was significantly higher than in the control groups; the collagen fibers per area around the pulmonary vessels was quite significantly lower and negatively correlated with the expression of MMP-2 by Spearman’s analysis. Our data indicated that the reticular fibers were deposited and disordered in the tumor tissues of the lungs in the removal groups, and the reticular fibers per area was higher than in the control groups. The tumor cells in the PALN of control groups were significantly higher than in the SiLN removal groups, and CD169+ and CD11c+ cells were also higher than in the SiLN removal groups. Altogether, surgical removal of the tumor-bearing lymph node promoted tumor metastasis through changing the niche in lung and liver. Treatment targeting the metastatic niche might be an effective strategy to prevent tumor metastasis, thereby possibly increasing the survival and reducing the incidence of metastasis in cancer patients.
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影响因子：
5.7
作者：
Miura Y;Mikada M;Ouchi T;Horie S;Takeda K;Yamaki T;Sakamoto M;Mori S;Kodama T
通讯作者：
Kodama T
癌症转移中lncRNA和microRNA之间的串扰：协调上皮间质可塑性
影响因子：
--
作者：
Cao MX;Jiang YP;Tang YL;Liang XH
通讯作者：
Liang XH
影响因子：
50.3
作者：
Pàez-Ribes M;Allen E;Hudock J;Takeda T;Okuyama H;Viñals F;Inoue M;Bergers G;Hanahan D;Casanovas O
通讯作者：
Casanovas O
影响因子：
50.3
作者：
Erler JT;Bennewith KL;Cox TR;Lang G;Bird D;Koong A;Le QT;Giaccia AJ
通讯作者：
Giaccia AJ
影响因子：
50.3
作者：
Liu, Yang;Cao, Xuetao
通讯作者：
Cao, Xuetao