Characterization of the melanoma brain metastatic niche in mice and humans.
Characterization of the melanoma brain metastatic niche in mice and humans.
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DOI：
10.1002/cam4.45
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发表时间：
2013-04
期刊：
影响因子：
4
通讯作者：
Gil, Ziv
中科院分区：
文献类型：
--
作者：
Amit, Moran;Laider-Trejo, Leonor;Shalom, Vardit;Shabtay-Orbach, Ayelet;Krelin, Yakov;Gil, Ziv
15% 的黑色素瘤患者会发生脑转移，且预后不佳。在这里，我们研究了小鼠和人类黑色素瘤脑转移的结构表型和基质反应。通过心内注射引入表达同源绿色荧光蛋白 (GFP) 的鼠 B16-F1 黑色素瘤克隆，并与人类样本进行体内检查。脑转移瘤的免疫荧光分析显示，F4/80+巨噬细胞/小胶质细胞在肿瘤前端最为丰富，但在肿瘤核心很少见，仅在血管周围发现（P = 0.01）。 CD3+ T 细胞中也发现了类似的浸润模式 (P < 0.01)。与 CD8+ T 细胞相比，浸润性 T 细胞明显为 CD4+（P < 0.001）。肿瘤前部的血管 (CD31+) 数量少于其中心（每个高倍视野 [HPF] 12 ± 1 条血管与 4 ± 0.6 条血管，P < 0.001）。相比之下，肿瘤前端血管较少，但前端直径明显较大（平均横截面积为8236 μm2 vs. 4617 μm2，P < 0.005）。这是首次对黑色素瘤脑转移进行比较分析，在小鼠模型和人类标本中显示出相似的基质反应。我们的结果验证了这种黑色素瘤脑转移小鼠模型在研究人类疾病机制方面的实用性。
Brain metastases occur in 15% of patients with melanoma and are associated with a dismal prognosis. Here, we investigate the architectural phenotype and stromal reaction of melanoma brain metastasis in mice and humans. A syngeneic, green fluorescence protein (GFP)-expressing murine B16-F1 melanoma clone was introduced via intracardiac injection, and was examined in vivo in comparison with human specimens. Immunofluorescence analyses of the brain metastases revealed that F4/80+ macrophages/microglia were most abundant at the tumor front, but rare in its core, where they were found only around blood vessels (P = 0.01). Similar pattern of infiltration was found in CD3+ T cells (P < 0.01). Infiltrating T cells were prominently CD4+ compared with CD8+ T cells (P < 0.001). Blood vessels (CD31+) were less abundant at the tumor front than in its center (12 ± 1 vs. 4 ± 0.6 vessels per high-power field [HPF], P < 0.001). In contrast, there were few vessels at the tumor front, but their diameter was significantly larger at the front (8236 μm2 vs. 4617 μm2 average cross-sectional area, P < 0.005). This is the first comparative analysis of melanoma brain metastases showing similar stromal reaction in murine models and human specimens. Our results validate the utility of this murine model of melanoma brain metastases for investigating the mechanism of the human disease.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
腋窝淋巴结中免疫细胞的特征可以预测乳腺癌中无疾病的生存。
影响因子：
15.8
作者：
Kohrt, HE;Nouri, N;Nowels, K;Johnson, D;Holmes, S;Lee, PP
通讯作者：
Lee, PP
影响因子：
4
作者：
Fitzgerald, Daniel P.;Palmieri, Diane;Hua, Emily;Hargrave, Elizabeth;Herring, Jeanne M.;Qian, Yongzhen;Vega-Valle, Eleazar;Weil, Robert J.;Stark, Andreas M.;Vortmeyer, Alexander O.;Steeg, Patricia S.
通讯作者：
Steeg, Patricia S.
影响因子：
2.5
作者：
Badie, B;Schartner, J
通讯作者：
Schartner, J
影响因子：
50.3
作者：
Blouw, B;Song, HQ;Bergers, G
通讯作者：
Bergers, G