Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis.
Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis.
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DOI：
10.1186/bcr2345
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Mukherjee P
中科院分区：
文献类型：
--
作者：
Das Roy L;Pathangey LB;Tinder TL;Schettini JL;Gruber HE;Mukherjee P
慢性炎症的部位通常与包括乳腺癌在内的各种恶性肿瘤的建立和生长有关。人类常见的炎症性疾病是自身免疫性关节炎（AA），其导致关节的炎症和畸形。与关节炎相关的其他全身效应包括增加的细胞浸润和肺部炎症。几项研究报告了AA和乳腺癌之间的统计学显著风险比。尽管这一知识已有十年之久，但从未有人质疑与AA相关的慢性炎症部位是否会产生一种环境，吸引肿瘤细胞回家并在发炎的骨骼和肺部生长，这些部位是乳腺癌转移的常见部位。为了确定自身免疫性关节炎诱导的慢性炎症是否有助于增加乳腺癌相关转移，我们在遗传上易于发展AA的SKG小鼠中产生乳腺肿瘤。使用两种乳腺癌细胞系，一种高转移性（4 T1）和另一种非转移性（TUBO）在乳腺脂肪垫中产生肿瘤。肺和骨转移和相关的炎症环境进行了评估，在关节炎与非关节炎小鼠。我们报告了三倍增加肺转移和骨转移的发病率显着增加关节炎和关节炎的小鼠相比，非关节炎对照组小鼠。我们还报告说，转移性乳腺癌细胞增加关节炎的严重程度，导致恶性循环，增加骨破坏和转移。促关节炎和关节炎小鼠肺和骨中嗜中性粒细胞和粒细胞浸润增强以及随后促炎细胞因子循环水平升高，如巨噬细胞集落刺激因子（M-CSF）、白细胞介素-17（IL-17）、白细胞介素-6（IL-6）、血管内皮生长因子（VEGF）和肿瘤坏死因子-α（TNF-α）可能导致转移增加。用抗IL 17+塞来昔布（一种抗炎药）治疗完全消除了转移的发展，并显著降低了原发性肿瘤负荷。这些数据显然对诊断为转移性乳腺癌的患者具有重要的临床意义，特别是在预后和治疗选择方面。
Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha) may contribute to the increased metastasis. Treatment with anti-IL17 + celecoxib, an anti-inflammatory drug completely abrogated the development of metastasis and significantly reduced the primary tumor burden. The data clearly has important clinical implications for patients diagnosed with metastatic breast cancer, especially with regards to the prognosis and treatment options.
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影响因子：
9
作者：
Byrnes, K;White, S;Li, BD
通讯作者：
Li, BD
影响因子：
4.4
作者：
Kryczek, Ilona;Wei, Shuang;Zou, Weiping
通讯作者：
Zou, Weiping
影响因子：
3.5
作者：
Jin, Di;Zhang, Lianjun;Zhao, Yong
通讯作者：
Zhao, Yong
DOI：
10.1073/pnas.0813306106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Hua, Min;Peluffo, Guillermo;Polyak, Kornelia
通讯作者：
Polyak, Kornelia
DOI：
10.1186/bcr1515
发表时间：
2006
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Hattrup CL;Gendler SJ
通讯作者：
Gendler SJ