GM-CSF production by glioblastoma cells has a functional role in eosinophil survival, activation, and growth factor production for enhanced tumor cell proliferation.
GM-CSF production by glioblastoma cells has a functional role in eosinophil survival, activation, and growth factor production for enhanced tumor cell proliferation.
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DOI：
10.4049/jimmunol.1001965
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发表时间：
2011-08-01
期刊：
影响因子：
--
通讯作者：
Bertics PJ
中科院分区：
文献类型：
--
作者：
Curran CS;Evans MD;Bertics PJ
目前，疗效有限的药物干预可用于治疗多形性胶质母细胞瘤（GBM），这是成人中最常见和最致命的原发性脑肿瘤。嗜酸性粒细胞是特应性疾病病理生物学中的关键免疫细胞，也发现其在某些肿瘤组织中积聚。特应性和GBM风险之间的负相关性表明嗜酸性粒细胞可能在某些肿瘤免疫反应中发挥功能性作用。为了评估嗜酸性粒细胞和GBM之间的潜在相互作用，将人原代血嗜酸性粒细胞与两种单独的人GBM衍生细胞系（A172、U87-MG）或在存在或不存在TNF-α的情况下生成的条件培养基一起培养。结果显示，差异嗜酸性粒细胞粘附和增加的生存与GBM细胞系的共培养。嗜酸性粒细胞对GBM细胞系条件培养基的反应包括增加的存活、活化、CD 11b表达和S100 A9释放。向GBM细胞培养物或条件培养基中添加GM-CSF中和抗体降低了嗜酸性粒细胞的粘附、存活和活化，将肿瘤细胞衍生的GM-CSF与肿瘤微环境中嗜酸性粒细胞的功能联系起来。据报道，地塞米松可抑制嗜酸性粒细胞的募集，缩小对比增强扫描的GBM病变，减少肿瘤细胞源性GM-CSF的产生。此外，在嗜酸性粒细胞条件培养基中培养GBM细胞增加了肿瘤细胞的活力，并且在GM-CSF存在下产生嗜酸性粒细胞条件培养基增强了该效果。这些数据支持在肿瘤促进/进展中GM-CSF产生肿瘤和嗜酸性粒细胞衍生的生长因子之间的旁分泌环的想法。
Medicinal interventions of limited efficacy are currently available for the treatment of glioblastoma multiforme (GBM), the most common and lethal primary brain tumor in adults. The eosinophil is a pivotal immune cell in the pathobiology of atopic disease that is also found to accumulate in certain tumor tissues. Inverse associations between atopy and GBM risk suggest that the eosinophil may play a functional role in certain tumor immune responses. To assess the potential interactions between eosinophils and GBM, human primary blood eosinophils were cultured with two separate human GBM-derived cell lines (A172, U87-MG) or conditioned media generated in the presence or absence of TNF-α. Results revealed differential eosinophil adhesion and increased survival in response to co-culture with GBM cell lines. Eosinophil responses to GBM cell line-conditioned media included increased survival, activation, CD11b expression and S100A9 release. Addition of GM-CSF neutralizing antibodies to GBM cell cultures or conditioned media reduced eosinophil adhesion, survival and activation, linking tumor cell-derived GM-CSF to the functions of eosinophils in the tumor microenvironment. Dexamethasone, which has been reported to inhibit eosinophil recruitment and shrink GBM lesions on contrast enhanced scans, reduced the production of tumor cell-derived GM-CSF. Furthermore, culture of GBM cells in eosinophil-conditioned media increased tumor cell viability, and generation of eosinophil-conditioned media in the presence of GM-CSF enhanced the effect. These data support the idea of a paracrine loop between GM-CSF producing tumors and eosinophil-derived growth factors in tumor promotion/progression.
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影响因子：
3.6
作者：
Bennicelli, J L;Guerry, D 4th
通讯作者：
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作者：
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DOI：
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发表时间：
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影响因子：
6.4
作者：
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通讯作者：
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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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DOI：
10.4049/jimmunol.0900634
发表时间：
2010-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bates ME;Sedgwick JB;Zhu Y;Liu LY;Heuser RG;Jarjour NN;Kita H;Bertics PJ
通讯作者：
Bertics PJ