Abstract
Abstract Introduction CXC chemokine receptor 4 was found dys-regulated in many different types of human cancers and correlated with poor prognosis of tumor metastasis and resistance to chemotherapy. Limited data show the effect of CXCR4 on the esophageal carcinoma cells, especially with influence of chemotheraputuc reagent-cisplatin. Methods CXCR4 was detected by FACs analysis in esophageal cell lines OE19, OE21, OE33, PT1590 and LN1590. Corronsponding cisplatin resistant cells were established after selection of cisplatin treatment and further confirmed by IC50 and ERCC1. SDF-1α and AMD3100 were used as CXCR4 stimulattion or inhibition. Subcutanous model of OE19 injection in Balb/c nude mice was established and followed by treatment with cisplatin twice a week via i.p injection. Tumors were collected for the further evaluation. Results Esophageal cell line OE19, PT1590 and LN1590 have detetable amount of CXCR4+ subpopulation cells as high as 2.8%±0.9, 0.7%± 0.9 and 1.0%±0.6, respectively. OE19, PT1590 and LN1590 cisplatin resistant subline displayed increased IC50 value of 48h cisplatin treatment from 6.0±1.3 to 12.2±1.0, 1.4±0.7 to 9.1±0.7 and 1.4±0.6 to 7.2±0.6 ug/ml along with a significant overexpression of ERCC1. Interestingly only OE19 and LN1590 cisplatin resistant cell lines showed a significant enreichment of CXCR4+ cells ( 12.1%± 2.5 Vs 2.8%±0.9; 4.2%± 1.1 Vs1.0%±0.6, p<0.05) as compared to parental cells. Meanwhile, side population cells were also increased in those cisplatin resistant variants. There is no difference on tumor weight in control group and cisplatin treatment group in vivo. The relative expression of CXCR4 will be further evaluated by realtime PCR on mRNA level and IHC on protein level. Conclusion Overexpression of CXCR4 is significantly associated with cisplatin-based chemotherapy resistance and might be a prognostic factor in esophageal cancer. Inhibition of CXCR4 might be a strategy to address the chemoresistance of EAC cell lines. Citation Format: Yue Zhao, Yan Wang, Christiane Bruns. The potential role of CXCR4 in cisplatin associated resistance in esophageal carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3751. doi:10.1158/1538-7445.AM2014-3751
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