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自然杀伤细胞可以通过 TRAIL/DR5 信号通路优先靶向前列腺癌干细胞样细胞。

NK Cells Can Preferentially Target Prostate Cancer Stem-like Cells via the TRAIL/DR5 Signaling Pathway.

机构信息

Graduate School of Food and Nutritional Sciences, Toyo University, Gunma 347-0193, Japan.

Graduate School of Science and Engineering, Toyo University, Saitama 350-8555, Japan.

出版信息

Biomolecules. 2021 Nov 16;11(11):1702. doi: 10.3390/biom11111702.

Abstract

BACKGROUND

The occurrence of androgen-dependent prostate cancer mainly depends on prostate cancer stem cells. To reduce the risk of androgen-dependent prostate cancer, the direct elimination of prostate cancer stem cells is important, but an elimination strategy has not yet been established. A previous study showed that natural killer (NK) cells can preferentially target cancer stem cells in several solid tumors except prostate cancer. In this context, this study was undertaken to investigate if NK cells can selectively attack androgen-dependent prostate cancer stem cells.

METHODS

Prostate cancer stem-like cells were separated from an androgen-dependent prostate cancer cell line (LNCaP) using a three-dimensional culture system. LNCaP stem-like cells or LNCaP cells were co-cultured with human NK cells (KHYG-1) for 24-72 h, and cell viability was determined using the WST-8 method. The expression of each protein in the cell membrane was evaluated through FACS analysis, and mRNA levels were determined using real-time PCR.

RESULTS

KHYG-1 cells had more potent cytotoxicity against LNCaP stem-like cells than LNCaP cells, and the potency of the cytotoxicity was strongly related to the TRAIL/DR5 cell death pathway.

CONCLUSION

NK cells can preferentially target prostate cancer stem-like cells via the TRAIL/DR5 pathway.

摘要

背景

雄激素依赖性前列腺癌的发生主要依赖于前列腺癌干细胞。为了降低雄激素依赖性前列腺癌的风险,直接消除前列腺癌干细胞非常重要,但尚未建立消除策略。先前的研究表明,自然杀伤 (NK) 细胞可以优先针对几种实体瘤(除前列腺癌外)中的癌症干细胞。在这种情况下,进行了这项研究,以调查 NK 细胞是否可以选择性攻击雄激素依赖性前列腺癌干细胞。

方法

使用三维培养系统从雄激素依赖性前列腺癌细胞系(LNCaP)中分离前列腺癌干细胞样细胞。将 LNCaP 干细胞样细胞或 LNCaP 细胞与人类 NK 细胞(KHYG-1)共培养 24-72 小时,使用 WST-8 法测定细胞活力。通过 FACS 分析评估细胞膜上每种蛋白的表达,并使用实时 PCR 测定 mRNA 水平。

结果

KHYG-1 细胞对 LNCaP 干细胞样细胞的细胞毒性比 LNCaP 细胞更强,细胞毒性的强度与 TRAIL/DR5 细胞死亡途径密切相关。

结论

NK 细胞可以通过 TRAIL/DR5 途径优先靶向前列腺癌干细胞样细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2461/8615937/98516d350046/biomolecules-11-01702-g001a.jpg

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