Mou Junjun, Zheng Wei, Wei Dong, Li Dalei, Fan Rong, Tang Qing
Department of Radiotherapy, Yantai Yuhuangding Hospital, Yantai, 264000, China.
Department of Gynecology, Yantai Yuhuangding Hospital, Yantai, 264000, China.
Heliyon. 2023 Aug 18;9(8):e19220. doi: 10.1016/j.heliyon.2023.e19220. eCollection 2023 Aug.
CD200-CD200R plays a critical role in regulating the human tumor microenvironment, but its role in cervical cancer remains unclear.
A total of 62 paraffin blocks of tumor tissues were collected from cervical cancer patients. Expression of CD200 and cathepsin K (CTSK) in cancer tissues and para-cancerous tissues was analyzed by immunohistochemistry. Stably transfected CD200 cells were established in HeLa and SiHa cells. Human THP-1 monocytes were induced to differentiate into M2 macrophages. HeLa and SiHa cells were cultured in conditioned medium from M2 macrophages to observe the effects of CD200-CD200R on invasion, CTSK, p65NF-κB, and cisplatin or paclitaxel sensitivity in cervical cancer cells. HeLa cells were injected to induce xenograft tumors in mice, and a CTSK inhibitor, MK-0822, was used to confirm the regulation of CTSK and paclitaxel sensitivity by CD200-CD200R in vivo.
A significant decrease in CD200 and CTSK expression was found in tumor cancer tissues compared with para-cancerous tissues. Only CD200 overexpression did not affect cervical cell invasion, but CD200-CD200R could enhance the cell invasion and resistance to cisplatin or paclitaxel. Meanwhile, expression of CTSK and p-p65NF-κB in cancer cells stably transfected with CD200 was obviously increased after culture in conditioned medium from M2 macrophages compared with transfection with the plasmid control. In vivo, CTSK inhibition significantly suppressed the effects of CD200-CD200R overexpression on the response to paclitaxel by suppressing the CTSK-mediated NF-κB pathway.
CD200-CD200R regulates CTSK-mediated NF-κB pathway to affect cisplatin or paclitaxel sensitivity in cervical cancer, which provides a possible immunotherapeutic target and combination strategy for advanced cervical cancer.
CD200-CD200R在调节人类肿瘤微环境中起关键作用，但其在宫颈癌中的作用仍不清楚。
从宫颈癌患者中收集了62个肿瘤组织石蜡块。通过免疫组织化学分析癌组织和癌旁组织中CD200和组织蛋白酶K（CTSK）的表达。在HeLa和SiHa细胞中建立稳定转染CD200的细胞。将人THP-1单核细胞诱导分化为M2巨噬细胞。将HeLa和SiHa细胞培养在M2巨噬细胞的条件培养基中，以观察CD200-CD200R对宫颈癌细胞侵袭、CTSK、p65NF-κB以及顺铂或紫杉醇敏感性的影响。将HeLa细胞注射到小鼠体内诱导异种移植瘤，并使用CTSK抑制剂MK-0822在体内证实CD200-CD200R对CTSK和紫杉醇敏感性的调节作用。
与癌旁组织相比，肿瘤癌组织中CD200和CTSK表达显著降低。仅CD200过表达不影响宫颈细胞侵袭，但CD200-CD200R可增强细胞侵袭及对顺铂或紫杉醇的抗性。同时，与质粒对照转染相比，用CD200稳定转染的癌细胞在M2巨噬细胞的条件培养基中培养后，CTSK和p-p65NF-κB的表达明显增加。在体内，CTSK抑制通过抑制CTSK介导的NF-κB途径显著抑制了CD200-CD200R过表达对紫杉醇反应的影响。
CD200-CD200R调节CTSK介导的NF-κB途径以影响宫颈癌对顺铂或紫杉醇的敏感性，这为晚期宫颈癌提供了一种可能的免疫治疗靶点和联合策略。
