Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.
Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.
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DOI：
10.1073/pnas.1417273112
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发表时间：
2015-03-31
影响因子：
11.1
通讯作者：
Kangawa K
中科院分区：
文献类型：
--
作者：
Nojiri T;Hosoda H;Tokudome T;Miura K;Ishikane S;Otani K;Kishimoto I;Shintani Y;Inoue M;Kimura T;Sawabata N;Minami M;Nakagiri T;Funaki S;Takeuchi Y;Maeda H;Kidoya H;Kiyonari H;Shioi G;Arai Y;Hasegawa T;Takakura N;Hori M;Ohno Y;Miyazato M;Mochizuki N;Okumura M;Kangawa K
术后癌症复发是治疗性癌症手术后的主要问题。围手术期全身性炎症诱导原发肿瘤释放的循环肿瘤细胞粘附于远处器官的血管内皮，这是血行转移的第一步。我们以前曾报道，心钠素（ANP）的管理在围手术期减少炎症反应，并有预防术后心肺并发症的肺癌手术。在这里，我们证明，肺癌手术后的癌症复发显着降低ANP治疗的患者比对照组患者（手术单独）。我们发现，ANP通过抑制内皮细胞的炎症反应，从而抑制癌细胞粘附到血管内皮细胞，从而防止癌症转移。大多数癌症患者死于转移性疾病。实体瘤的手术切除作为治愈患者的初步尝试;然而，手术通常伴有创伤，这可以通过引起肿瘤细胞脱离到血流中或诱导全身炎症或两者来促进早期复发。我们以前曾报道，心钠素（ANP）的管理在围手术期减少炎症反应，并有预防术后心肺并发症的肺癌手术。在这里，我们证明，根治性手术后，癌症复发显着降低ANP治疗的患者比对照组患者（手术单独）。已知ANP特异性结合NPR 1 [也称为鸟苷酸环化酶-A（GC-A）受体]。在小鼠模型中，我们发现不表达GC-A的肿瘤细胞（即，与对照小鼠相比，血管内皮特异性GC-A基因敲除小鼠中B16小鼠黑色素瘤细胞）对肺的作用增加，而血管内皮特异性GC-A转基因小鼠中则减少。我们研究了ANP对脂多糖治疗小鼠肿瘤转移的影响，脂多糖模拟手术应激诱导的全身炎症。ANP通过抑制炎症促进的E-选择素表达，抑制癌细胞与肺动脉和微血管内皮细胞的粘附。这些结果表明，ANP通过抑制肿瘤细胞与发炎的内皮细胞的粘附来防止癌症转移。
Postoperative cancer recurrence is a major problem following curative cancer surgery. Perioperative systemic inflammation induces the adhesion of circulating tumor cells released from the primary tumor to the vascular endothelium of distant organs, which is the first step in hematogenous metastasis. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here, we demonstrate that cancer recurrence after lung cancer surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). We show that ANP prevents cancer metastasis by suppressing the inflammatory reaction of endothelial cells, thereby inhibiting cancer cell adhesion to vascular endothelial cells. Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A–nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.
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影响因子：
3.1
作者：
Jersmann, HPA;Hii, CST;Ferrante, A
通讯作者：
Ferrante, A
DOI：
10.1016/0006-291x(84)91077-5
发表时间：
1984-01-01
影响因子：
3.1
作者：
KANGAWA, K;MATSUO, H
通讯作者：
MATSUO, H
影响因子：
3.7
作者：
Ferri, LE;Law, S;Wong, J
通讯作者：
Wong, J
影响因子：
56.9
作者：
BEVILACQUA, MP;STENGELIN, S;SEED, B
通讯作者：
SEED, B
影响因子：
20.3
作者：
Laeubli, Heinz;Spanaus, Katharina-Susanne;Borsig, Lubor
通讯作者：
Borsig, Lubor