Roles of C-reactive protein and LOX-1 on cancer and myeloid-derived suppressor cells in the progression of uterine cervical cancer.

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Tác giả: Takashi Akazawa, Tomoya Ekawa, Tsuyoshi Hisa, Shoji Kamiura, Tadashi Kimura, Naoko Komura, Seiji Mabuchi, Michihide Maeda, Shinya Matsuzaki, Yu Mizote, Harumi Nakamura, Mina Sakata, Tomoyuki Sasano, Hideaki Tahara, Tsuyoshi Takiuchi

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: England : Scientific reports , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 711438

We investigated clinical implications of CRP and its receptor, LOX-1, in cervical cancer progression and the underlying mechanisms. Clinical data from 121 patients with cervical cancer administered definitive radiotherapy were analyzed to investigate the relationship among pretreatment serum CRP levels, tumor LOX-1 expression, and treatment outcomes. Clinical samples, cervical cancer cell lines, and mouse xenograft models of cervical cancer were employed to elucidate the mechanisms for CRP-mediated progression of cervical cancer, focusing on LOX-1 expression on cancer and myeloid-derived suppressor (MDSCs) cells. Patients with elevated pretreatment CRP levels showed significantly shorter overall survival when their cervical tumor expressed LOX-1. In contrast, elevated pretreatment CRP levels had no prognostic relevance in patients with cervical tumors not expressing LOX-1. CRP treatment of LOX1-expressing cervical cancer cells induced ERK phosphorylation and stimulated cell proliferation in vitro. In vivo, CRP treatment promoted the progression of LOX-1-expressing cervical cancer. In vitro, it stimulated MDSC survival and augmented their suppressive activity. However, the tumor-promoting effects of CRP were minimal in tumors not expressing LOX-1. In conclusion, CRP facilitates progression of LOX-1-expressing cervical cancer by stimulating LOX-1 and its downstream effectors in cancer cells and MDSCs. Novel treatments targeting CRP or LOX-1 may be against LOX1-expressing cancer.
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