Abstract

Purpose

Cancer stem cells (CSCs) are relatively resistant to radiation compared to their non-tumorigenic progeny. Ionizing radiation (IR) can expand the pool of CSCs that leads to more aggressive cancers, but the reason underlying CSC-induced cancer aggressiveness after radiation therapy remains unclear. To understand this, we investigated the phenotypic and molecular characteristics of sphere cells formed from IR-treated patient-derived xenograft (PDX) lung adenocarcinoma tumors.

Materials and methods

After treatment with various modes of IR, we collected tumors from PDX mice and successfully obtained sphere cells. To compare tumorigenicity, we performed migration, invasion, and mouse transplantation assays with sphere cells from each group. To investigate the molecular features, we used a cDNA microarray and compared gene expression among groups.

Results and conclusions

Tumorigenicity assays revealed that sphere cells from 2- or 5-Gy IR-treated tumors more aggressive than sphere cells from non-IR treated tumors. Microarray results showed that SERPIB4 and CCL2 were upregulated in sphere cells from IR-treated tumors compared to that in sphere cells from non-IR treated tumors. Interestingly, these genes are related to immune reactions in cancer. Taken together, our results suggest that the aggressiveness of sphere cells obtained after IR treatment is related to resistance, and provide new opportunities for exploring targeted therapies to overcome common radioresistance.

中文翻译：

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用电离辐射治疗的肺腺癌患者异种移植模型衍生的球状细胞特征。

摘要

目的

癌症干细胞（CSC）与其非致瘤性后代相比，相对抗辐射。电离辐射（IR）可以扩大CSC的范围，从而导致更具侵略性的癌症，但是目前尚不清楚放射治疗后CSC诱发癌症侵袭性的原因。为了理解这一点，我们调查了由IR治疗的患者源异种移植（PDX）肺腺癌肿瘤形成的球状细胞的表型和分子特征。

材料和方法

经过各种模式的IR治疗后，我们从PDX小鼠中收集了肿瘤并成功获得了球状细胞。为了比较致瘤性，我们对每组的球状细胞进行了迁移，侵袭和小鼠移植试验。为了研究分子特征，我们使用了cDNA微阵列并比较了各组之间的基因表达。

结果与结论

致瘤性分析显示，来自2或5 Gy IR治疗的肿瘤的球细胞比来自未经IR治疗的肿瘤的球细胞更具侵略性。微阵列结果显示，与未经IR治疗的肿瘤的球状细胞相比，来自IR治疗的肿瘤的球状细胞中SERPIB4和CCL2被上调。有趣的是，这些基因与癌症中的免疫反应有关。综上所述，我们的结果表明，IR治疗后获得的球状细胞的侵袭性与耐药性有关，并为探索靶向疗法克服常见的放射抵抗提供了新的机会。