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.
复制标题
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
中科院分区:
文献类型:
--
作者:
Liao,Shan;Bouta,EchoeM;Morris,LindaM;Jones,Dennis;Jain,RakeshK;Padera,TimothyP
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.