Inducible expression of a prostate cancer-testis antigen, SSX-2, following treatment with a DNA methylation inhibitor
Inducible expression of a prostate cancer-testis antigen, SSX-2, following treatment with a DNA methylation inhibitor
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DOI：
10.1002/pros.20665
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发表时间：
2007-12-01
期刊：
影响因子：
2.8
通讯作者：
McNeel, Douglas G.
中科院分区：
文献类型：
--
作者：
Dubovsky, Jason A.;McNeel, Douglas G.
背景。主动免疫疗法是一种正在开发的前列腺癌新疗法。这些疗法成功的关键是识别适当的靶抗原。我们一直在寻求在前列腺癌患者中鉴定免疫学识别的蛋白质，特别是癌症睾丸抗原（CTA），这将是合理的靶抗原。方法。使用之前报道的 29 种不同 CTA 组，我们使用 98 名前列腺癌患者和 50 名健康男性献血者对照的血清来检测 CTA 特异性 IgG。然后我们进一步评估了前列腺癌细胞系和组织中一种抗原 SSX-2 的表达。结果。我们在至少 1/98 的前列腺癌患者中鉴定出了 NY-ESO-1、LAGE-1、NFX-2 和 SSX-2 特异性的 IgG。我们证明SSX-2是一种前列腺CTA，其表达与转移性前列腺癌相关。此外，我们报告用 DNA 甲基化抑制剂 5-aza-2'-deoxycytidine 处理至少两种人类前列腺癌细胞系可诱导 SSX-2 的表达。相反，用5-氮杂-2'-脱氧胞苷处理正常前列腺上皮细胞系(RWPE-1)不会诱导SSX-2表达。结论。我们的研究结果表明，SSX-2 可以进一步作为前列腺癌的免疫治疗靶点，并且可以利用 5-aza-2'-脱氧胞苷治疗与免疫治疗方法相结合来调节抗原表达。
BACKGROUND. Active immunotherapies are one approach being developed as novel treatments for prostate cancer. Critical to the success of these therapies is the identification of appropriate target antigens. We have been seeking to identify immunologically recognized proteins, cancer-testis antigens (CTA) in particular, in patients with prostate cancer that would be rational target antigens.METHODS. Using a previously reported panel of 29 different CTA, we used sera from 98 patients with prostate cancer and 50 healthy male blood donor controls to detect CTA-specific IgG. We then further evaluated the expression of one antigen, SSX-2, in prostate cancer cell lines and tissues.RESULTS. We identified IgG specific for NY-ESO-1, LAGE-1, NFX-2, and SSX-2 in at least 1/98 individuals with prostate cancer. We demonstrated that SSX-2 is a prostate CTA, and its expression is associated with metastatic prostate cancer. In addition, we report that the treatment of at least two human prostate cancer cell lines with the DNA methylation inhibitor 5-aza-2'-deoxycytidine induced the expression of SSX-2. In contrast, treatment of a normal prostate epithelial cell line (RWPE-1) with 5-aza-2'-deoxycytidine did not induce SSX-2 expression.CONCLUSIONS. Our findings suggest that SSX-2 could be further pursued as an immunotherapeutic target in prostate cancer, and that treatment with 5-aza-2'-deoxycytidine could be exploited to modulate antigen expression in combination with immunotherapeutic approaches.