Functional role of endothelial adhesion molecules in the early stages of brain metastasis.
Functional role of endothelial adhesion molecules in the early stages of brain metastasis.
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DOI：
10.1093/neuonc/not222
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发表时间：
2014-04
期刊：
影响因子：
15.9
通讯作者：
Sibson NR
中科院分区：
文献类型：
--
作者：
Soto MS;Serres S;Anthony DC;Sibson NR
通常与白细胞运输相关的细胞粘附分子（CAM）也已被证明在肿瘤转移至非CNS部位中发挥重要作用。然而，CAM在脑转移中所起的作用在很大程度上尚未探索。已知白细胞向脑的募集是非常非典型的，并且外周组织中的疾病机制不能外推至脑。在这里，我们已经建立了12个关键CAM的时空表达在2个不同的脑转移模型中的肿瘤种植的初始阶段。将BALB/c或SCID小鼠心内注射（105个细胞/100 μL磷酸盐缓冲盐水，分别具有4 T1-GFP或MDA 231 BR-GFP细胞（n = 4-6/组）），并通过免疫组织化学和免疫荧光共定位测定CAM的表达。E-选择素、VCAM-1、ALCAM、ICAM-1、VLA-4和β4整合素在肿瘤种植早期的内皮表达显著增加。同时，这些粘附分子的天然配体在体外和体内的转移性肿瘤细胞上均高度表达。这些配体中的两种显示出特别高的肿瘤细胞表达（ALCAM和VLA-4），因此确定了它们在肿瘤接种中的功能作用。ALCAM或VLA-4的抗体中和显著减少脑内的肿瘤种植（肿瘤数量/mm 2脑减少>60%; P <0.05 -0.01）。这些发现表明，ALCAM/ALCAM和VLA-4/VCAM-1的相互作用在脑转移种植的早期阶段发挥重要的功能作用。此外，这项工作确定了一个特定的配体-受体相互作用的子集，可能会产生新的治疗和诊断脑转移的目标。
Cellular adhesion molecules (CAMs), which are normally associated with leukocyte trafficking, have also been shown to play an essential role in tumor metastasis to non-CNS sites. However, the role played by CAMs in brain metastasis is largely unexplored. It is known that leukocyte recruitment to the brain is very atypical and that mechanisms of disease in peripheral tissues cannot be extrapolated to the brain. Here, we have established the spatiotemporal expression of 12 key CAMs in the initial phases of tumor seeding in 2 different models of brain metastasis. BALB/c or SCID mice were injected intracardially (105 cells/100 μL phosphate-buffered saline with either 4T1-GFP or MDA231BR-GFP cells, respectively (n = 4–6/group), and expression of the CAMs was determined by immunohistochemistry and immunofluorescence colocalisation. Endothelial expression of E-selectin, VCAM-1, ALCAM, ICAM-1, VLA-4, and β4 integrin was markedly increased early in tumor seeding. At the same time, the natural ligands to these adhesion molecules were highly expressed on the metastatic tumor cells both in vitro and in vivo. Two of these ligands showed particularly high tumor cell expression (ALCAM and VLA-4), and consequently their functional role in tumor seeding was determined. Antibody neutralization of either ALCAM or VLA-4 significantly reduced tumor seeding within the brain (>60% decrease in tumor number/mm2 brain; P < .05–0.01). These findings suggest that ALCAM/ALCAM and VLA-4/VCAM-1 interactions play an important functional role in the early stages of metastasis seeding in the brain. Moreover, this work identifies a specific subset of ligand-receptor interactions that may yield new therapeutic and diagnostic targets for brain metastasis.
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影响因子：
2.9
作者：
BAO, L;PIGOTT, R;TARIN, D
通讯作者：
TARIN, D
影响因子：
3.8
作者：
Sipos, Eszter;Chen, Lei;Toborek, Michal
通讯作者：
Toborek, Michal
DOI：
10.1186/1478-811x-6-10
发表时间：
2008-12-04
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Strell, Carina;Entschladen, Frank
通讯作者：
Entschladen, Frank
影响因子：
6
作者：
Lorger, Mihaela;Felding-Habermann, Brunhilde
通讯作者：
Felding-Habermann, Brunhilde
影响因子：
6.4
作者：
Brooks, Kimberly. L.;Coleman, Elaine J.;Vitetta, Ellen S.
通讯作者：
Vitetta, Ellen S.