Bisgin Atil, Meng Wen-Jian, Adell Gunnar, Sun Xiao-Feng
Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Medical Genetics Department of Balcali Clinics and Hospital, Faculty of Medicine, Cukurova University, Adana, Turkey.
J Oncol. 2019 Jan 21;2019:5689464. doi: 10.1155/2019/5689464. eCollection 2019.
CD200 imparts an immunoregulatory signal through its receptor, CD200R1, leading to the suppression of tumor specific immunity. The mechanism of CD200:CD200R1 signaling pathway is still uncertain. Our aim was to investigate the expression and localization of CD200 and its receptor CD200R1 and their clinical significance in rectal cancer patients. We examined the immunohistochemical expressions and localizations of CD200 and CD200R1 in 140 rectal cancer patients. Among the patients, 79 underwent the preoperative radiotherapy and the others were untreated prior to the surgery. In addition, 121 matched normal rectal mucosa samples were evaluated. The results of immunohistochemical analysis showed a strikingly high level of CD200 in tumor cells (p=0.001) and CD200R1 expression in normal mucosal epithelium and stromal cells. Importantly, CD200R1 was overexpressed in stromal cells of the metastatic cancer patients compared to patients without metastases (p=0.002). More than that, 87% of metastatic patients had a phenotype of upregulated CD200 in tumor cells accompanied by overexpressed CD200R1 in stromal cells. In addition, low levels of CD200 were correlated with improved overall survival in untreated patients. We showed that tumor-stroma communication through CD200 and its receptor interaction is selected in patients with high risk of relapse. High levels of these molecules support instigation of the far and local metastatic nest that provides solid ground for metastasis. Our current data also disclose a mechanism by which CD200:CD200R1 affects tumor progression and may strengthen the feasibility of targeting CD200 or CD200R1 as anticancer strategy.
CD200通过其受体CD200R1传递免疫调节信号，导致肿瘤特异性免疫受到抑制。CD200:CD200R1信号通路的机制仍不明确。我们的目的是研究CD200及其受体CD200R1在直肠癌患者中的表达、定位及其临床意义。我们检测了140例直肠癌患者中CD200和CD200R1的免疫组化表达及定位。其中79例患者接受了术前放疗，其余患者在手术前未接受治疗。此外，还评估了121例配对的正常直肠黏膜样本。免疫组化分析结果显示，肿瘤细胞中CD200水平显著升高（p = 0.001），正常黏膜上皮和基质细胞中CD200R1表达阳性。重要的是，与无转移患者相比，转移癌患者基质细胞中CD200R1过表达（p = 0.002）。此外，87%的转移患者肿瘤细胞中CD200上调，同时基质细胞中CD200R1过表达。另外，未接受治疗患者中CD200水平较低与总生存期改善相关。我们发现，复发风险高的患者中，通过CD200及其受体相互作用实现的肿瘤-基质通讯被选择。这些分子的高水平支持远处和局部转移灶的形成，为转移提供了坚实基础。我们目前的数据还揭示了CD200:CD200R1影响肿瘤进展的机制，并可能增强将CD200或CD200R1作为抗癌策略的可行性。
