Simultaneous irradiation of fibroblasts and carcinoma cells repress the secretion of soluble factors able to stimulate carcinoma cell migration.
Simultaneous irradiation of fibroblasts and carcinoma cells repress the secretion of soluble factors able to stimulate carcinoma cell migration.
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成纤维细胞和癌细胞的同时辐照抑制能够刺激癌细胞迁移的可溶性因子的分泌。
DOI：
10.1371/journal.pone.0115447
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Vozenin MC
中科院分区：
文献类型：
--
作者：
Arshad A;Deutsch E;Vozenin MC
基质介导的伤口愈合信号可能与肿瘤微环境产生的信号具有相似性，并且它们的调节可能影响肿瘤对各种抗癌治疗（包括放射治疗）的反应。因此，我们进行了这项研究，以评估间质和癌细胞之间的串扰，通过遗传调节的间质和辐射的放射治疗。我们发现，成纤维细胞无论其RhoB状态不调节TC-1的内在放射敏感性，但产生能够改变肿瘤细胞命运的扩散因子。我们发现Wt和RhoB缺陷的成纤维细胞分别通过TGF-β1和MMP介导的不同机制刺激TC-1迁移。最后，我们发现同时照射成纤维细胞和TC-1通过抑制TGF-β和MMP分泌而废除促迁移表型。最后一个结果与临床情况高度相关，并表明与目前的观点相反，辐照的基质不会增强癌细胞迁移，并可被操纵以促进抗肿瘤免疫应答。
Stroma mediated wound healing signals may share similarities with the ones produced by tumor’s microenvironment and their modulation may impact tumor response to the various anti-cancer treatments including radiation therapy. Therefore we conducted this study, to assess the crosstalk between stromal and carcinoma cells in response to radiotherapy by genetic modulation of the stroma and irradiation. We found that fibroblasts irrespective of their RhoB status do not modulate intrinsic radiosensitivity of TC-1 but produce diffusible factors able to modify tumor cell fate. Then we found that Wt and RhoB deficient fibroblasts stimulated TC-1 migration through distinct mechanisms which are TGF-β1 and MMP-mediated respectively. Lastly, we found that simultaneous irradiation of fibroblasts and TC-1 abrogated the pro-migratory phenotype by repression of TGF-β and MMP secretion. This last result is highly relevant to the clinical situation and suggests that conversely to, the current view; irradiated stroma would not enhance carcinoma migration and could be manipulated to promote anti-tumor immune response.
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