Inducible Nitric Oxide Synthase and CD11b+Gr1+ Cells Impair Lymphatic Contraction of Tumor-Draining Lymphatic Vessels.

Inducible Nitric Oxide Synthase and CD11b+Gr1+ Cells Impair Lymphatic Contraction of Tumor-Draining Lymphatic Vessels.
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诱导型一氧化氮合酶和 CD11b Gr1 细胞会损害肿瘤引流淋巴管的淋巴收缩。

DOI:
10.1089/lrb.2018.0013
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发表时间:
2019
影响因子:
1.4
通讯作者:
Padera,TimothyP
Padera,TimothyP
中科院分区:
医学4区
文献类型:
--
作者:
Liao,Shan;Bouta,EchoeM;Morris,LindaM;Jones,Dennis;Jain,RakeshK;Padera,TimothyP

文献摘要

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背景:转移性肿瘤细胞通过淋巴管扩散并定植于引流淋巴结(LN)。它是已知的,肿瘤诱导淋巴管生成,以提高淋巴转移和转移癌细胞进行淋巴流向LNs.Methods和结果:在这里,我们研究了收集淋巴管收缩血管引流转移性肿瘤使用活体显微镜的分子和细胞调控。在肿瘤引流集合淋巴管中,我们发现血管收缩受到抑制。诱导型一氧化氮合酶阳性和CD 11b +Gr1+髓样细胞浸润瘤周组织在抑制淋巴管收缩中起关键作用。用抗Gr1抗体耗尽Gr1+细胞改善了肿瘤引流淋巴管的收缩。此外,诱导肿瘤细胞死亡恢复nukemic.Conclusions淋巴收缩:这些研究结果表明,肿瘤有助于调节淋巴运输的可逆方式,进一步调查受损的淋巴运输在癌症进展中的作用。
Background:Metastatic tumor cells spread through lymphatic vessels and colonize draining lymph nodes (LNs). It is known that tumors induce lymphangiogenesis to enhance lymphatic metastasis and that metastatic cancer cells are carried by lymph flow to LNs.Methods and Results:Here, we investigated the molecular and cellular regulation of collecting lymphatic vessel contraction in vessels draining a metastatic tumor using intravital microscopy. In tumor-draining collecting lymphatic vessels, we found vessel contraction was suppressed. The infiltration of peritumor tissue by inducible nitric oxide synthase positive and CD11b+Gr1+myeloid cells played a critical role in the suppression of lymphatic contraction. Depletion of Gr1+cells with an anti-Gr1 antibody improved contraction of tumor-draining lymphatic vessels. In addition, inducing tumor cell death restored lymphatic contraction in nude mice.Conclusions:These findings indicate that tumors contribute to regulation of lymphatic transport in a reversible manner, warranting further investigation into the role of impaired lymphatic transport in cancer progression.