Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization.
Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization.
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DOI：
10.1007/s10585-008-9193-z
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发表时间：
2008
影响因子：
4
通讯作者：
Steeg, Patricia S.
中科院分区：
文献类型：
--
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.
肿瘤细胞与微环境之间的相互作用对肿瘤的形成和转移至关重要。中枢神经系统是肿瘤转移的“避难所”，导致确诊患者预后不良。脑转移的发生率正在增加；然而，对脑和转移细胞之间的相互作用知之甚少。在脑转移的实验模型系统中，使用MDA-MB-231人乳腺癌细胞的亚系进行了脑病理学检查。这一结果与16例切除的乳腺癌脑转移瘤的分析结果进行了比较。实验性转移瘤好发于特定的脑区，其分布与临床病例相似。在231-BR模型和人类标本中，Ki67的表达表明转移是高度增殖的(~50%)。在这两组肿瘤中都观察到很少的细胞凋亡。在模型系统中，转移瘤引发脑部炎症反应，转移瘤周围广泛的反应性胶质增生。同样，在人脑转移瘤的内部肿块中也发现了大量的胶质细胞。体外共培养表明，胶质细胞诱导的转移细胞增殖增加了~5倍(P<；0.001)，表明脑组织分泌有利于肿瘤细胞生长的因子。用于在肿瘤细胞和周围神经胶质细胞之间传递信号的分子可能为脑转移瘤提供一种新的治疗靶点。
Interactions between tumor cells and the microenvironment are crucial to tumor formation and metastasis. The central nervous system serves as a “sanctuary” site for metastasis, resulting in poor prognosis in diagnosed patients. The incidence of brain metastasis is increasing; however, little is known about interactions between the brain and metastatic cells. Brain pathology was examined in an experimental model system of brain metastasis, using a subline of MDA-MB-231 human breast cancer cells. The results were compared with an analysis of sixteen resected human brain metastases of breast cancer. Experimental metastases formed preferentially in specific brain regions, with a distribution similar to clinical cases. In both the 231-BR model, and in human specimens, Ki67 expression indicated that metastases were highly proliferative (~50%). Little apoptosis was observed in either set of tumors. In the model system, metastases elicited a brain inflammatory response, with extensive reactive gliosis surrounding metastases. Similarly, large numbers of glial cells were found within the inner tumor mass of human brain metastases. In vitro co-cultures demonstrated that glia induced a ~5-fold increase in metastatic cell proliferation (P < 0.001), suggesting that brain tissue secretes factors conducive to tumor cell growth. Molecules used to signal between tumor cells and the surrounding glia could provide a new avenue of therapeutic targets for brain metastases.
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影响因子：
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作者：
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通讯作者：
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