NK Cells Can Target Castration-resistant Prostate Cancer Stem Cells With the Involvement of Degranulation Pathway.

IF 1.7 4区医学 Q4 ONCOLOGY

Anticancer research Pub Date : 2025-08-01 DOI:10.21873/anticanres.17682

Asuka Hattori, Taiga Seki, Kazunori Kato, Nantiga Virgona, Yuichi Miyakoshi, Kakeru Kohno, Tomohiro Yano

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引用次数: 0

Abstract

Background/aim: Castration-resistant prostate cancer (CRPC) is lethal and refractory to therapy. To reduce the risk of CRPC, a direct elimination strategy of cancer stem cells is needed, but a promising approach to target cancer stem cells has not yet been established. Natural killer (NK) cells are known to exhibit potent cytotoxic activity against cancer stem cells. In this study, we aimed to clarify whether CRPC cells with stemness characteristics are more sensitive to NK cells than CRPC cells without stemness features.

Materials and methods: PC-3 stem-like (PC3-stem) cells separated from the CRPC cell line PC-3 (PC3) using a three-dimensional tumor sphere culture method. Each type of tumor cells (PC3 or PC3-stem) were then co-cultured with the human NK-like cell line KHYG-1, and cell viability was determined using the WST-8 method and crystal violet staining. mRNA levels were determined using real-time PCR, and the expression of each protein was evaluated using flow cytometry and ELISA.

Results: KHYG-1 cells exhibited more potent cytotoxicity against PC3-stem cells than PC3 cells. In addition, the mechanism that leads to the NK cell cytotoxicity favoring toward PC3-stem cells was associated with the NKG2D-MICA/B-mediated degranulation pathway.

Conclusion: These observations raise the possibility that targeting CRPC stem cells with NK cells may lead to the establishment of novel therapeutic strategies for the suppression of CRPC development.

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NK细胞靶向去势抵抗性前列腺癌干细胞与脱颗粒通路的关系

背景/目的：去势抵抗性前列腺癌（CRPC）是一种致命且难以治疗的癌症。为了降低CRPC的风险，需要一种直接消除癌症干细胞的策略，但一种有希望的靶向癌症干细胞的方法尚未建立。已知自然杀伤细胞（NK）对癌症干细胞具有强效的细胞毒活性。在本研究中，我们旨在阐明具有干性特征的CRPC细胞是否比不具有干性特征的CRPC细胞对NK细胞更敏感。材料与方法：采用三维肿瘤球培养法从CRPC细胞系PC-3 （PC3）中分离出PC-3干样细胞（PC3-stem）。将各类型肿瘤细胞（PC3或PC3-干细胞）与人nk样细胞系KHYG-1共培养，采用WST-8法和结晶紫染色测定细胞活力。实时荧光定量PCR检测mRNA水平，流式细胞术和ELISA检测各蛋白表达。结果：KHYG-1细胞对PC3干细胞的杀伤作用强于PC3细胞。此外，导致NK细胞毒性倾向于pc3干细胞的机制与NKG2D-MICA/ b介导的脱颗粒途径有关。结论：这些观察结果提出了用NK细胞靶向CRPC干细胞可能导致建立抑制CRPC发展的新治疗策略的可能性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.