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髓源性抑制细胞产生的前列腺素E2诱导子宫颈癌中的癌症干细胞。

Prostaglandin E2 produced by myeloid-derived suppressive cells induces cancer stem cells in uterine cervical cancer.

作者信息

Kuroda Hiromasa, Mabuchi Seiji, Yokoi Eriko, Komura Naoko, Kozasa Katsumi, Matsumoto Yuri, Kawano Mahiru, Takahashi Ryoko, Sasano Tomoyuki, Shimura Kotaro, Kodama Michiko, Hashimoto Kae, Sawada Kenjiro, Morii Eiichi, Kimura Tadashi

机构信息

Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.

Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.

出版信息

Oncotarget. 2018 Nov 20;9(91):36317-36330. doi: 10.18632/oncotarget.26347.

Abstract

Myeloid-derived suppressor cells (MDSCs) enhance tumor progression by suppressing tumor-specific T cell responses, stimulating tumor angiogenesis, or promoting tumor cell metastasis. However, the biology of MDSCs have not been fully investigated. In the current study, we investigated the role of MDSCs in inducing cancer stem-like cells and explored a clinically feasible approach for targeting MDSCs-mediated cancer stem-like cells induction. and experiments revealed that MDSCs induced by tumor-derived G-CSF enhanced the stemness of cervical cancer cells by producing Prostaglandin E2 (PGE2). We also demonstrated that anti-Gr-1 neutralizing antibody or celecoxib inhibited the induction of cancer stem-like cells and enhanced the efficacy of cisplatin in cervical cancer. In clinical samples, MDSCs, PGE2, and CSCs had positive correlations. In conclusion, G-CSF-induced MDSCs enhance the stemness of uterine cervical cancer cells by producing PGE2. Targeting MDSCs or PGE2 might be a reasonable strategy for enhancing the efficacies of treatments. .

摘要

髓源性抑制细胞(MDSCs)通过抑制肿瘤特异性T细胞反应、刺激肿瘤血管生成或促进肿瘤细胞转移来促进肿瘤进展。然而,MDSCs的生物学特性尚未得到充分研究。在本研究中,我们研究了MDSCs在诱导癌症干细胞样细胞中的作用,并探索了一种针对MDSCs介导的癌症干细胞样细胞诱导的临床可行方法。实验表明,肿瘤来源的G-CSF诱导的MDSCs通过产生前列腺素E2(PGE2)增强了宫颈癌细胞的干性。我们还证明,抗Gr-1中和抗体或塞来昔布可抑制癌症干细胞样细胞的诱导,并增强顺铂对宫颈癌的疗效。在临床样本中,MDSCs、PGE2和癌症干细胞样细胞呈正相关。总之,G-CSF诱导的MDSCs通过产生PGE2增强了子宫颈癌细胞的干性。靶向MDSCs或PGE2可能是提高治疗效果的合理策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e484/6284736/7136da4e5a26/oncotarget-09-36317-g003.jpg

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