Exploring the role of CHI3L1 in "pre-metastatic" lungs of mammary tumor-bearing mice.
Exploring the role of CHI3L1 in "pre-metastatic" lungs of mammary tumor-bearing mice.
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DOI：
10.3389/fphys.2013.00392
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发表时间：
2013
影响因子：
4
通讯作者：
Iragavarapu-Charyulu VL
中科院分区：
文献类型：
--
作者：
Libreros S;Garcia-Areas R;Keating P;Carrio R;Iragavarapu-Charyulu VL
在乳腺癌患者中，几丁质酶-3-样-1(CHI3L1)水平升高与预后不良、无复发间期短和生存率低有关。乳腺癌常常转移到肺部。我们假设，在“转移前”肺微环境中表达的分子可以通过提供生长和血管生成因子来支持新移民的肿瘤细胞。已知巨噬细胞通过释放促血管生成分子在肿瘤生长中发挥重要作用。利用小鼠乳腺肿瘤模型，我们先前已经证明，在肿瘤进展过程中，荷瘤小鼠的乳腺肿瘤细胞和脾巨噬细胞都比正常对照组小鼠表达更高水平的CHI3L1。然而，CHI3L1在肺微环境中诱导巨噬细胞血管生成以支持新到达的乳腺癌细胞的作用尚不清楚。在本研究中，我们检测了CHI3L1在支气管肺泡灌洗巨噬细胞和间质巨噬细胞中的表达，以调节血管生成，从而支持新进入肺的乳腺肿瘤细胞的生长。在这里，我们表明，重组小鼠CHI3L1体外处理肺巨噬细胞后，促进了促血管生成分子CCL2、CXCL2和MMP-9的表达。我们和其他人之前已经表明，抑制CHI3L1会减少血管生成分子的产生。在这项研究中，我们探讨了体内注射甲壳素微粒是否对荷瘤小鼠肺组织中CHI3L1和促血管生成分子的表达有影响。我们发现，甲壳素微粒治疗减少了CHI3L1和促血管生成分子在“转移”肺中的表达。这些研究表明，靶向CHI3L1可能是一种潜在的治疗药物，可以抑制血管生成，从而可能抑制肿瘤的生长和转移。
Elevated levels of chitinase-3-like-1 (CHI3L1) are associated with poor prognosis, shorter recurrence-free intervals and low survival in breast cancer patients. Breast cancer often metastasizes to the lung. We hypothesized that molecules expressed in the “pre-metastatic” lung microenvironment could support the newly immigrant tumor cells by providing growth and angiogenic factors. Macrophages are known to play an important role in tumor growth by releasing pro-angiogenic molecules. Using mouse mammary tumor models, we have previously shown that during neoplastic progression both the mammary tumor cells and splenic macrophages from tumor-bearing mice express higher levels of CHI3L1 compared to normal control mice. However, the role of CHI3L1 in inducing angiogenesis by macrophages at the pulmonary microenvironment to support newly arriving breast cancer cells is not yet known. In this study, we determined the expression of CHI3L1 in bronchoalveolar lavage macrophages and interstitial macrophages in regulating angiogenesis that could support the growth of newly immigrant mammary tumor cells into the lung. Here we show that in vitro treatment of pulmonary macrophages with recombinant murine CHI3L1 resulted in enhanced expression of pro-angiogenic molecules including CCL2, CXCL2, and MMP-9. We and others have previously shown that inhibition of CHI3L1 decreases the production of angiogenic molecules. In this study, we explored if in vivo administration of chitin microparticles has an effect on the expression of CHI3L1 and pro-angiogenic molecules in the lungs of mammary tumor-bearing mice. We show that treatment with chitin microparticles decreases the expression of CHI3L1 and pro-angiogenic molecules in the “metastatic” lung. These studies suggest that targeting CHI3L1 may serve as a potential therapeutic agent to inhibit angiogenesis and thus possibly tumor growth and metastasis.
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影响因子：
5.5
作者：
Kogiso, Mari;Nishiyama, Akihito;Shibata, Yoshimi
通讯作者：
Shibata, Yoshimi
影响因子：
5.7
作者：
Faibish M;Francescone R;Bentley B;Yan W;Shao R
通讯作者：
Shao R
影响因子：
8
作者：
Kawada, M.;Seno, H.;Kanda, K.;Nakanishi, Y.;Akitake, R.;Komekado, H.;Kawada, K.;Sakai, Y.;Mizoguchi, E.;Chiba, T.
通讯作者：
Chiba, T.
影响因子：
15.9
作者：
Arenberg, DA;Keane, MP;Strieter, RM
通讯作者：
Strieter, RM
DOI：
10.1084/jem.20081271
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee CG;Hartl D;Lee GR;Koller B;Matsuura H;Da Silva CA;Sohn MH;Cohn L;Homer RJ;Kozhich AA;Humbles A;Kearley J;Coyle A;Chupp G;Reed J;Flavell RA;Elias JA
通讯作者：
Elias JA