Arthritis augments breast cancer metastasis: role of mast cells and SCF/c-Kit signaling.
Arthritis augments breast cancer metastasis: role of mast cells and SCF/c-Kit signaling.
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DOI：
10.1186/bcr3412
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发表时间：
2013-04-11
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;Curry JM;Sahraei M;Besmer DM;Kidiyoor A;Gruber HE;Mukherjee P
乳腺癌仍然是美国女性癌症相关死亡的第二大原因。转移不仅受到恶性细胞内在遗传变化的调节，而且还受到微环境的调节，特别是与慢性炎症相关的微环境。我们最近报道，患有自身免疫性关节炎的小鼠骨和肺转移的发生率显著增加，并且与乳腺癌相关的生存率降低。在这项研究中，我们评估了转移增加的机制。我们使用了两种小鼠模型;一种是注射转移性乳腺癌细胞（4 T1）后发生自发性自身免疫性关节炎的小鼠（SKG小鼠），另一种是注射II型胶原以诱导自身免疫性关节炎的自发性乳腺癌小鼠（MMTV-PyV MT小鼠）。监测肥大细胞水平和转移。首先，我们证实了患有关节炎的乳腺肿瘤小鼠的骨和肺转移发生率明显高于非关节炎小鼠。接下来，我们发现在关节炎小鼠的原发性肿瘤中肥大细胞的募集增加，这有助于转移。接下来，我们报告说，没有任何肿瘤的关节炎小鼠在骨骼和肺部有更多的肥大细胞，这可能是在关节炎小鼠中观察到的肺和骨转移增强的根本原因。接下来，我们发现，一旦肿瘤细胞占据转移性小生境（骨和肺），它们会进一步增加小生境内的肥大细胞数量，并有助于增强转移。这可能主要是由于肥大细胞上存在的c-Kit受体与肿瘤细胞上表达的干细胞因子（SCF，ckit的配体）的相互作用。最后，我们发现，用抗ckit抗体靶向SCF/cKit相互作用减少了肥大细胞的分化，从而减少了转移。这是第一份报告表明，肥大细胞可能发挥关键作用，重塑不仅是肿瘤微环境，而且转移小生境，以促进有效的转移，通过SCF/cKit相互作用，在乳腺癌关节炎。
Breast cancer remains the second leading cause of cancer-related deaths for women in the United States. Metastasis is regulated not only by intrinsic genetic changes in malignant cells, but also by the microenvironment, especially those associated with chronic inflammation. We recently reported that mice with autoimmune arthritis have significantly increased incidence of bone and lung metastasis and decreased survival associated with breast cancer. In this study, we evaluated the mechanism underlying the increased metastasis. We used two mouse models; one that develops spontaneous autoimmune arthritis (SKG mice) injected with metastatic breast cancer cells (4T1), and another that develops spontaneous breast cancer (MMTV-PyV MT mice) injected with type II collagen to induce autoimmune arthritis. Mast cell levels and metastasis were monitored. First, we confirmed that breast tumor-bearing arthritic mice have a significantly higher incidence of bone and lung metastasis than do their nonarthritic counterparts. Next, we showed increased recruitment of mast cells within the primary tumor of arthritic mice, which facilitates metastasis. Next, we report that arthritic mice without any tumors have higher numbers of mast cells in the bones and lungs, which may be the underlying cause for the enhanced lung and bone metastases observed in the arthritic mice. Next, we showed that once the tumor cells populate the metastatic niches (bones and lungs), they further increase the mast cell population within the niche and assist in enhancing metastasis. This may primarily be due to the interaction of c-Kit receptor present on mast cells and stem cell factor (SCF, the ligand for ckit) expressed on tumor cells. Finally, we showed that targeting the SCF/cKit interaction with an anti-ckit antibody reduces the differentiation of mast cells and consequently reduces metastasis. This is the first report to show that mast cells may play a critical role in remodeling not only the tumor microenvironment but also the metastatic niche to facilitate efficient metastasis through SCF/cKit interaction in breast cancer with arthritis.
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影响因子：
3.8
作者：
Das Roy, Lopamudra;Ghosh, Sriparna;Mukherjee, Pinku
通讯作者：
Mukherjee, Pinku
影响因子：
4.4
作者：
D Basu, Gargi;Tinder, Teresa L.;Mukherjee, Pinku
通讯作者：
Mukherjee, Pinku
DOI：
10.1186/bcr2345
发表时间：
2009
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Das Roy L;Pathangey LB;Tinder TL;Schettini JL;Gruber HE;Mukherjee P
通讯作者：
Mukherjee P
影响因子：
5.5
作者：
Ji, Jianguang;Liu, Xiangdong;Sundquist, Jan
通讯作者：
Sundquist, Jan
影响因子：
5.3
作者：
GUY, CT;CARDIFF, RD;MULLER, WJ
通讯作者：
MULLER, WJ