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Enhanced CXCL12/CXCR4 signaling increases tumor progression in radiation-resistant pancreatic cancer

ABSTRACT: Pancreatic cancer (PaCa) has one of the poorest prognoses among gastrointestinal cancers because of rapid development of treatment resistance, which renders chemotherapy and radiotherapy no longer effective. As the mechanism by which PaCa becomes resistant to radiotherapy is unknown, we established radiation-resistant PaCa cell lines to investigate the factors involved in radiation resistance. We investigated the role of the C-X-C motif chemokine 12 (CXCL12)/ C-X-C chemokine receptor type 4 (CXCR4) axis in radiation resistance in PaCa and the effect of a CXCR4 antagonist on radiation-resistant PaCa cell lines. As confirmed by immunofluorescence staining, RT-qPCR, and Western blotting, the expression of CXCR4 was higher in the radiation-resistant PaCa cell lines than 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 co-culture 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. We believe this result will help develop treatments for PaCa.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193616 | GEO | 2022/01/14

REPOSITORIES: GEO

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Enhanced CXCL12/CXCR4 signaling increases tumor progression in radiation-resistant pancreatic cancer

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