CD248 facilitates tumor growth via its cytoplasmic domain.
CD248 facilitates tumor growth via its cytoplasmic domain.
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DOI：
10.1186/1471-2407-11-162
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发表时间：
2011-05-08
期刊：
影响因子：
3.8
通讯作者：
Conway EM
中科院分区：
文献类型：
--
作者：
Maia M;DeVriese A;Janssens T;Moons M;Lories RJ;Tavernier J;Conway EM
基质成纤维细胞参与肿瘤生长的容许环境的发展，但治疗靶向成纤维细胞的分子途径定义不清。CD 248，也称为内皮唾液酸蛋白或肿瘤内皮标志物1（TEM 1），是在活化的成纤维细胞上表达的跨膜糖蛋白。我们最近发现，CD 248的胞质结构域在促进关节炎小鼠模型的炎症反应中很重要。其他人已经报道了小鼠中的CD 248基因失活导致肿瘤生长受到抑制。我们假设CD 248的保守胞质结构域在调节肿瘤生长中是重要的。产生缺乏CD 248胞质结构域的小鼠（CD 248 CyD/CyD），并在肿瘤模型中进行评价，将结果与野生型小鼠（CD 248 WT/WT）进行比较。与CD 248 WT/WT小鼠中的反应相比，CD 248 CyD/CyD小鼠中T241纤维肉瘤和刘易斯肺癌的生长显著降低。肿瘤大小与CD 248缺陷小鼠相似。来自CD 248 CyD/CyD成纤维细胞的条件培养基在支持T241纤维肉瘤细胞存活方面不太有效。除了我们之前观察到的活化基质金属蛋白酶（MMP）-9释放减少外，CD 248 CyD/CyD成纤维细胞还具有PDGF-BB诱导的迁移受损，并表达更高的肿瘤抑制因子transgelin（SM 22 α）、Hes和Hey 1转录本。由CD 248的胞质结构域调节的多种途径突出了其作为治疗癌症的治疗靶点的潜力。
Stromal fibroblasts participate in the development of a permissive environment for tumor growth, yet molecular pathways to therapeutically target fibroblasts are poorly defined. CD248, also known as endosialin or tumor endothelial marker 1 (TEM1), is a transmembrane glycoprotein expressed on activated fibroblasts. We recently showed that the cytoplasmic domain of CD248 is important in facilitating an inflammatory response in a mouse model of arthritis. Others have reported that CD248 gene inactivation in mice results in dampened tumor growth. We hypothesized that the conserved cytoplasmic domain of CD248 is important in regulating tumor growth. Mice lacking the cytoplasmic domain of CD248 (CD248CyD/CyD) were generated and evaluated in tumor models, comparing the findings with wild-type mice (CD248WT/WT). As compared to the response in CD248WT/WT mice, growth of T241 fibrosarcomas and Lewis lung carcinomas was significantly reduced in CD248CyD/CyD mice. Tumor size was similar to that seen with CD248-deficient mice. Conditioned media from CD248CyD/CyD fibroblasts were less effective at supporting T241 fibrosarcoma cell survival. In addition to our previous observation of reduced release of activated matrix metalloproteinase (MMP)-9, CD248CyD/CyD fibroblasts also had impaired PDGF-BB-induced migration and expressed higher transcripts of tumor suppressor factors, transgelin (SM22α), Hes and Hey1. The multiple pathways regulated by the cytoplasmic domain of CD248 highlight its potential as a therapeutic target to treat cancer.
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影响因子：
64.5
作者：
Fischer, Christian;Jonckx, Bart;Carmeliet, Peter
通讯作者：
Carmeliet, Peter
影响因子：
50.3
作者：
Blouw, B;Song, HQ;Bergers, G
通讯作者：
Bergers, G
影响因子：
3.7
作者：
Efeyan, Alejo;Murga, Matilde;Serrano, Manuel
通讯作者：
Serrano, Manuel
DOI：
10.1016/j.biocel.2008.02.011
发表时间：
2009-03-01
影响因子：
4
作者：
Assinder, Stephen J.;Stanton, Jo-Ann L.;Prasad, Priya D.
通讯作者：
Prasad, Priya D.
影响因子：
7.3
作者：
Franco OE;Shaw AK;Strand DW;Hayward SW
通讯作者：
Hayward SW