Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan, Republic of China.
Mol Cancer. 2013 Oct 5;12(1):115. doi: 10.1186/1476-4598-12-115.
CD164 (endolyn), a sialomucin, has been reported to play a role in the proliferation, adhesion, and differentiation of hematopoietic stem cells. The potential association of CD164 with tumorigenicity remains unclear.
The clinicopathological correlation of ovarian cancer with CD164 was assessed in a 97-patient tumor tissue microarray. Overexpression or silence CD164 was to analyze the effect of CD164 on the proliferation, colony formation and apoptosis via a mouse xenograft and western blotting analysis. The subcellular localization of CD164 was collected in the immunohistochemical and confocal analysis.
Our data demonstrated that higher expression levels of CD164 were identified in malignant ovarian cancer cell lines, such as SKOV3 and HeyA8. The clinicopathological correlation analysis showed that the upregulation of CD164 protein was significantly associated with tumor grade and metastasis. The overexpression of CD164 in human ovarian epithelial surface cells promoted cellular proliferation and colony formation and suppressed apoptosis. These tumorigenicity effects of CD164 were reconfirmed in a mouse xenograft model. We also found that the overexpression of CD164 proteins increased the amounts of CXCR4 and SDF-1α and activated the SDF-1α/CXCR4 axis, inducing colony and sphere formation. Finally, we identified the subcellular localization of CD164 in the nucleus and cytosol and found that nuclear CD164 might be involved in the regulation of the activity of the CXCR4 promoter.
Our findings suggest that the increased expression of CD164 is involved in ovarian cancer progression via the SDF-1α/CXCR4 axis, which promotes tumorigenicity. Thus, targeting CD164 may serve as a potential ovarian cancer biomarker, and targeting CD164 may serve as a therapeutic modality in the management of high-grade ovarian tumors.
CD164（endolyn）是一种唾液酸粘蛋白，据报道它在造血干细胞的增殖、黏附和分化中发挥作用。CD164 与致瘤性的潜在关联尚不清楚。
在 97 例肿瘤组织微阵列中评估了 CD164 与卵巢癌的临床病理相关性。通过小鼠异种移植和 Western blot 分析，过表达或沉默 CD164 以分析 CD164 对增殖、集落形成和细胞凋亡的影响。在免疫组织化学和共聚焦分析中收集 CD164 的亚细胞定位。
我们的数据表明，CD164 在恶性卵巢癌细胞系（如 SKOV3 和 HeyA8）中的表达水平较高。临床病理相关性分析表明，CD164 蛋白的上调与肿瘤分级和转移显著相关。在人卵巢上皮表面细胞中过表达 CD164 可促进细胞增殖、集落形成并抑制凋亡。在小鼠异种移植模型中，也证实了 CD164 的这些致瘤作用。我们还发现，CD164 蛋白的过表达增加了 CXCR4 和 SDF-1α 的量，并激活了 SDF-1α/CXCR4 轴，诱导集落和球体形成。最后，我们确定了 CD164 在细胞核和细胞质中的亚细胞定位，并发现核 CD164 可能参与调节 CXCR4 启动子的活性。
我们的研究结果表明，CD164 的表达增加通过 SDF-1α/CXCR4 轴参与卵巢癌的进展，从而促进致瘤性。因此，靶向 CD164 可能成为卵巢癌的潜在生物标志物，靶向 CD164 可能成为治疗高级别卵巢肿瘤的一种治疗方法。
Zotero 插件
