CD200-CD200R affects cisplatin and paclitaxel sensitivity by regulating cathepsin K-mediated p65 NF-κB signaling in cervical cancer.

Abstract

Background:

CD200-CD200R plays a critical role in regulating the human tumor microenvironment, but its role in cervical cancer remains unclear.

Methods:

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.

Results:

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.

Conclusions:

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.

• Authors: Junjun Mou, Wei Zheng, Dong Wei, Dalei Li, Rong Fan, Qing Tang
• Journal: Heliyon (Heliyon) Vol. 9 Issue 8 Pg. e19220 (Aug 2023) ISSN: 2405-8440 [Print] England
• PMID: 37654464 (Publication Type: Journal Article)
• Copyright: © 2023 The Authors.