Enhanced CXCL12/CXCR4 signaling increases tumor progression in radiation-resistant pancreatic cancer
Enhanced CXCL12/CXCR4 signaling increases tumor progression in radiation-resistant pancreatic cancer
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DOI：
10.3892/or.2022.8279
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发表时间：
2022-04-01
期刊：
影响因子：
4.2
通讯作者：
Takiguchi, Shuji
中科院分区：
文献类型：
--
作者：
Kato, Tomokatsu;Matsuo, Yoichi;Takiguchi, Shuji
胰腺癌(PACA)是所有胃肠道肿瘤中预后最差的肿瘤之一，其原因是治疗耐药的快速发展，使得化疗和放射治疗不再有效。然而，PACA对放射治疗产生抵抗的机制尚不清楚。在这里，我们建立了抗辐射的PACA细胞系，以研究与辐射抗性有关的因素。研究C-X-C基序趋化因子配体12(CXCL12)/C-X-C趋化因子受体4型(CXCR4)轴在PACA辐射抗性中的作用以及CXCR4拮抗剂对辐射抗性PACA细胞株的影响。免疫荧光染色、逆转录定量聚合酶链式反应和Western blotting证实，CXCR4在辐射耐受的PACA细胞系中的表达高于正常PACA细胞系。抗辐射的PACA细胞株的侵袭能力强于正常细胞，CXCL12处理和与成纤维细胞共培养可增强这种增强的侵袭能力，这种增强的侵袭能力可被CXCR4拮抗剂AMD070抑制。CXCR4拮抗剂处理后的照射可抑制耐辐射的PACA细胞系的定植。综上所述，CXCL12/CXCR4轴可能参与了PACA的辐射抵抗。这些发现可能有助于开发新的PACA治疗方法。
Pancreatic cancer (PaCa) exhibits one of the poorest prognoses among all gastrointestinal cancers due to the rapid development of treatment resistance, which renders chemotherapy and radiotherapy no longer effective. However, the mechanisms through which PaCa becomes resistant to radiotherapy are unknown. Here, we established radiation-resistant PaCa cell lines to investigate the factors involved in radiation resistance. The role of the C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis in radiation resistance in PaCa and the effects of a CXCR4 antagonist on radiation-resistant PaCa cell lines were investigated. As confirmed by immunofluorescence staining, reverse transcription quantitative polymerase chain reaction, and western blotting, the expression of CXCR4 was higher in radiation-resistant PaCa cell lines than that noted in normal PaCa cell lines. The invasion ability of radiation-resistant PaCa cell lines was greater than that of normal cell lines and was enhanced by CXCL12 treatment and coculture with fibroblasts; this enhanced invasion ability was suppressed by the CXCR4 antagonist AMD070. Irradiation after treatment with the CXCR4 antagonist suppressed the colonization of radiation-resistant PaCa cell lines. In conclusion, the CXCL12/CXCR4 axis may be involved in the radiation resistance of PaCa. These findings may facilitate the development of novel treatments for PaCa.