Abstract
BackgroundCD164 (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.MethodsThe 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.ResultsOur 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.ConclusionsOur 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.
Highlights
Ovarian carcinomas are among the most lethal gynecological malignancies for women in the world [1,2]
The CXCR4 chemokine receptor has been implicated in many malignancies [14,15], and the SDF1α/CXCR4 axis has been shown to be involved in several aspects of tumor progression, including angiogenesis, metastasis and survival [16,17,18,19,20]
CD164 is highly expressed in ovarian cancer cell lines and tissues and serves as a prognostic marker To address whether CD164 is involved in ovarian tumorigenesis, we measured the expression of CD164 in some ovarian cancer cell lines and the normal ovarian cell line, human ovarian surface epithelial (hOSE), by immunoblotting analysis
Summary
Ovarian carcinomas are among the most lethal gynecological malignancies for women in the world [1,2]. Studies have shown that CD164 may serve as a signaling receptor that regulates proliferation, adhesion and migration in hematopoietic stem and progenitor cells [11,12]. The CXCR4 chemokine receptor has been implicated in many malignancies [14,15], and the SDF1α/CXCR4 axis has been shown to be involved in several aspects of tumor progression, including angiogenesis, metastasis and survival [16,17,18,19,20]. CD164 associates with the chemokine receptor CXCR4 [13], possibly as a coreceptor for the CXCR4 ligand SDF-1α. These results reveal that CD164 may be the key molecule in the modulation of the tumor progression.
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