Collectin-11 promotes cancer cell proliferation and tumor growth.
Collectin-11 promotes cancer cell proliferation and tumor growth.
复制标题
DOI：
10.1172/jci.insight.159452
复制
发表时间：
2023-03-08
期刊：
影响因子：
8
通讯作者：
Li, Ke
中科院分区：
文献类型：
--
作者：
Wang, Jia-Xing;Cao, Bo;Ma, Ning;Wu, Kun-Yi;Chen, Wan-Bing;Wu, Weiju;Dong, Xia;Liu, Cheng-Fei;Gao, Ya-Feng;Diao, Teng-Yue;Min, Xiao-Yun;Yong, Qing;Li, Zong-Fang;Zhou, Wuding;Li, Ke
凝集素-11（Collectin-11，CL-11）是近年来发现的一种可溶性C型凝集素，在胚胎发育、宿主防御、自身免疫和纤维化等方面具有独特的作用。在这里，我们报告CL-11在癌细胞增殖和肿瘤生长中也起着重要作用。在皮下注射中，发现Colec 11-/-小鼠的黑色素瘤生长受到抑制。B16黑素瘤模型。细胞和分子分析显示，CL-11对于黑色素瘤细胞增殖、血管生成、建立更具免疫抑制性的肿瘤微环境以及黑色素瘤内巨噬细胞重编程为M2表型至关重要。体外分析表明，CL-11可以激活酪氨酸激酶受体（EGFR，HER 3）和ERK，JNK和AKT信号通路，并对小鼠黑色素瘤细胞增殖具有直接刺激作用。此外，阻断CL-11（用L-岩藻糖处理）可抑制小鼠中的黑色素瘤生长。对开放数据集的分析显示，COLEC 11基因表达在人类黑色素瘤中上调，并且COLEC 11高表达具有生存率差的趋势。CL-11在体外也对黑色素瘤和其他几种类型的癌细胞中的人肿瘤细胞增殖具有直接刺激作用。总体而言，我们的研究结果为我们的知识提供了第一个证据，即CL-11是一种关键的肿瘤生长促进蛋白，也是一种有前途的肿瘤生长治疗靶点。
Collectin-11 (CL-11) is a recently described soluble C-type lectin that has distinct roles in embryonic development, host defence, autoimmunity, and fibrosis. Here we report that CL-11 also plays an important role in cancer cell proliferation and tumor growth. Melanoma growth was found to be suppressed in Colec11–/– mice in a s.c. B16 melanoma model. Cellular and molecular analyses revealed that CL-11 is essential for melanoma cell proliferation, angiogenesis, establishment of more immunosuppressive tumor microenvironment, and the reprogramming of macrophages to M2 phenotype within melanomas. In vitro analysis revealed that CL-11 can activate tyrosine kinase receptors (EGFR, HER3) and ERK, JNK, and AKT signaling pathways and has a direct stimulatory effect on murine melanoma cell proliferation. Furthermore, blockade of CL-11 (treatment with L-fucose) inhibited melanoma growth in mice. Analysis of open data sets revealed that COLEC11 gene expression is upregulated in human melanomas and that high COLEC11 expression has a trend toward poor survival. CL-11 also had direct stimulatory effects on human tumor cell proliferation in melanoma and several other types of cancer cells in vitro. Overall, our findings provide the first evidence to our knowledge that CL-11 is a key tumor growth–promoting protein and a promising therapeutic target in tumor growth.
登录
查看更多内容
影响因子：
14.9
作者：
Babicki S;Arndt D;Marcu A;Liang Y;Grant JR;Maciejewski A;Wishart DS
通讯作者：
Wishart DS
DOI：
10.1056/nejmoa1504030
发表时间：
2015-07-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Larkin J;Chiarion-Sileni V;Gonzalez R;Grob JJ;Cowey CL;Lao CD;Schadendorf D;Dummer R;Smylie M;Rutkowski P;Ferrucci PF;Hill A;Wagstaff J;Carlino MS;Haanen JB;Maio M;Marquez-Rodas I;McArthur GA;Ascierto PA;Long GV;Callahan MK;Postow MA;Grossmann K;Sznol M;Dreno B;Bastholt L;Yang A;Rollin LM;Horak C;Hodi FS;Wolchok JD
通讯作者：
Wolchok JD
影响因子：
158.5
作者：
LERNER, AB;MCGUIRE, JS
通讯作者：
MCGUIRE, JS
影响因子：
158.5
作者：
Larkin, J.;Chiarion-Sileni, V.;Wolchok, J. D.
通讯作者：
Wolchok, J. D.
影响因子：
8.8
作者：
Hoppener, Diederik J.;Nierop, Pieter M. H.;Verhoef, Cornelis
通讯作者：
Verhoef, Cornelis