UVB-irradiated apoptotic cells induce accelerated growth of co-implanted viable tumor cells in immune competent mice
UVB-irradiated apoptotic cells induce accelerated growth of co-implanted viable tumor cells in immune competent mice
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DOI：
10.3109/08916934.2012.754433
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发表时间：
2013-08-01
期刊：
影响因子：
3.5
通讯作者：
Munoz, Luis E.
中科院分区：
文献类型：
--
作者：
Chaurio, Ricardo;Janko, Christina;Munoz, Luis E.
实体瘤的存在是排斥、耐受和再生之间复杂平衡的结果，其中肿瘤细胞与宿主免疫系统细胞的相互作用对最终结果有很大贡献。在这里，我们报告了一个模型，其中致命的UVB照射的细胞导致加速生长的活肿瘤细胞在体外和同种异体免疫小鼠。单独UVB照射的肿瘤细胞不形成肿瘤，并且不能诱导对相同同种异体肿瘤的第二次攻击的耐受性。我们的数据显示，在大量接种UVB照射的肿瘤细胞中，垂死细胞在促进少数存活肿瘤细胞加速肿瘤细胞生长方面具有重要作用。这发生在活的和垂死/死亡的肿瘤细胞非常接近时，表明移动的因子有助于生长促进。凋亡细胞的抗炎和促生长特性基于几种独立的效应。UVB照射的凋亡细胞直接释放生长促进活性，并且凋亡细胞的巨噬细胞清除伴随着IL 10、TGF β和PGE 2的分泌。甚至在垂死的异源细胞中也观察到生长促进，这意味着保守的机制。未来的实验应该集中在体内产生的死亡肿瘤细胞对存活肿瘤细胞生长的影响，这对癌症治疗有一定的影响。
The presence of a solid tumor is the result of a complex balance between rejection, tolerance and regeneration in which the interactions of tumor cells with cells of the host immune system contribute strongly to the final outcome. Here we report on a model where lethally UVB-irradiated cells cause accelerated growth of viable tumor cells in vitro and in allogeneic immune competent mice. UVB-irradiated tumor cells alone did not form tumors and failed to induce tolerance for a second challenge with the same allogeneic tumor. Our data show an important role for dying cells in promoting accelerated tumor cell growth of a small number of viable tumor cells in a large inoculum of UVB-irradiated tumor cells. This occurs when viable and dying/dead tumor cells are in close proximity, suggesting that mobile factors contribute to growth promotion. The anti-inflammatory and growth promoting properties of apoptotic cells are based on several independent effects. UVB-irradiated apoptotic cells directly release a growth promoting activity and clearance by macrophages of apoptotic cells is accompanied by the secretion of IL10, TGF beta, and PGE2. Growth promotion is even observed with dying heterologous cells implying a conserved mechanism. Future experiments should focus on the effects of dying tumor cells generated in vivo on the outgrowth of surviving tumor cells which is prone to have implications for cancer therapy.