Induction of proinflammatory mediators by CHI3L1 is reduced by chitin treatment: decreased tumor metastasis in a breast cancer model.
Induction of proinflammatory mediators by CHI3L1 is reduced by chitin treatment: decreased tumor metastasis in a breast cancer model.
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DOI：
10.1002/ijc.26379
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发表时间：
2012-07-15
影响因子：
6.4
通讯作者：
Iragavarapu-Charyulu, Vijaya
中科院分区：
文献类型：
--
作者：
Libreros, Stephania;Garcia-Areas, Ramon;Shibata, Yoshimi;Carrio, Roberto;Torroella-Kouri, Marta;Iragavarapu-Charyulu, Vijaya
播散性转移占乳腺癌死亡人数的 90% 以上。最近，一种称为几丁质酶 3 样蛋白 1 (CHI3L1) 的糖蛋白血清水平升高与转移性乳腺癌患者的不良预后和较短的生存期相关。在这项研究中，我们发现荷瘤小鼠血浆中 CHI3L1 水平升高，并且肿瘤细胞和免疫细胞都表达和分泌 CHI3L1。然而，CHI3L1的生物学和生理功能仍不清楚。我们证明，虽然 CHI3L1 对干扰素-γ (IFN-γ) 的表达具有抑制作用，但 CHI3L1 上调促炎介质、C-趋化因子配体 2 (CCL2)、趋化因子 CX 基序配体 2 (CXCL2) 和基质金属蛋白酶-9 (MMP-9)，所有这些都有助于肿瘤生长和转移。我们发现，体外通过 siRNA 抑制 CHI3L1 可以抑制巨噬细胞产生 CCL2、CXCL2 和 MMP-9。用几丁质（β-(1-4)-聚-N-乙酰 D-葡萄糖胺）、TH1 佐剂和 CHI3L1 配体对患有乳腺肿瘤的小鼠进行体内治疗，可促进免疫效应功能，增加 IFN-γ 的产生，并减少 CCL2、CXCL2 和 MMP-9 的表达。对患有乳腺肿瘤的小鼠体内施用几丁质可显着减少肺转移。这些研究表明，CHI3L1 在肿瘤进展中发挥作用，并且几丁质可以抑制 CHI3L1 的多效作用，支持了 CHI3L1 是治疗乳腺癌的有用治疗靶点的观点。
Disseminated metastasis accounts for over 90% of breast cancer deaths. Recently, elevated serum levels of a glycoprotein known as chitinase-3 like-protein-1 (CHI3L1) has been correlated with poor prognosis and shorter survival of patients with metastatic breast cancer. In this study, we show that there are increased levels of CHI3L1 in plasma of tumor-bearing mice and that both tumor cells and immune cells express and secrete CHI3L1. However, the biological and physiological functions of CHI3L1 are still unclear. We demonstrate that while CHI3L1 has an inhibitory role in the expression of interferon-gamma (IFN-γ), CHI3L1 up-regulates pro-inflammatory mediators, C-chemokine ligand 2 (CCL2), Chemokine CX motif ligand 2 (CXCL2) and matrix metalloproteinase-9 (MMP-9) all of which contribute to tumor growth and metastasis. We found that in vitro inhibition of CHI3L1 by siRNA suppressed the production of CCL2, CXCL2 and MMP-9 by macrophages. In vivo treatment of mammary tumor-bearing mice with chitin (β-(1–4)-poly-N-acetyl D-glucosamine), a TH1 adjuvant and a ligand for CHI3L1, promoted immune effector functions with increased production of IFN-γ and decreased CCL2, CXCL2 and MMP-9 expression. In vivo administration of chitin to mammary tumor-bearing mice significantly decreased lung metastasis. These studies show that CHI3L1 plays a role in tumor progression and that chitin can inhibit the pleiotropic effects of CHI3L1 giving support to the idea that CHI3L1 is a useful therapeutic target for treatment of breast cancer.
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DOI：
10.1084/jem.188.12.2357
发表时间：
1998-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hung K;Hayashi R;Lafond-Walker A;Lowenstein C;Pardoll D;Levitsky H
通讯作者：
Levitsky H
影响因子：
5.5
作者：
Kogiso, Mari;Nishiyama, Akihito;Shibata, Yoshimi
通讯作者：
Shibata, Yoshimi
影响因子：
4.4
作者：
Da Silva, Carla A.;Chalouni, Cecile;Elias, Jack A.
通讯作者：
Elias, Jack A.
DOI：
10.1097/aci.0b013e3283306533
发表时间：
2009-10
影响因子：
2.8
作者：
Ober C;Chupp GL
通讯作者：
Chupp GL
影响因子：
5.7
作者：
Faibish M;Francescone R;Bentley B;Yan W;Shao R
通讯作者：
Shao R