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Updated: Oct 12, 2025

Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
Published on: March 14, 2014
NK Cells Can Preferentially Target Prostate Cancer Stem-like Cells via the TRAIL/DR5 Signaling Pathway
Taiga Seki1, Yui Shimizu2, Kyota Ishii1
1Graduate School of Food and Nutritional Sciences, Toyo University, Gunma 347-0193, Japan.
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.
Insights
Natural killer (NK) cells show enhanced cytotoxicity against prostate cancer stem cells. This targeted elimination via the TRAIL/DR5 pathway offers a potential strategy for treating androgen-dependent prostate cancer.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Androgen-dependent prostate cancer relies on cancer stem cells.
- Eliminating prostate cancer stem cells is crucial but lacks established strategies.
- Natural killer (NK) cells target stem cells in other tumors but not yet prostate cancer.
Purpose of the Study:
- To investigate the potential of NK cells to selectively target androgen-dependent prostate cancer stem cells.
- To explore NK cell-mediated elimination strategies for prostate cancer stem cells.
Main Methods:
- Prostate cancer stem-like cells were isolated from LNCaP cells using 3D culture.
- Co-culture assays with LNCaP stem-like cells and human NK cells (KHYG-1) were performed.
- Cell viability (WST-8), protein expression (FACS), and mRNA levels (real-time PCR) were analyzed.
Main Results:
- NK cells (KHYG-1) exhibited greater cytotoxicity against prostate cancer stem-like cells compared to standard LNCaP cells.
- The enhanced cytotoxicity was significantly linked to the TRAIL/DR5 cell death pathway.
Conclusions:
- NK cells demonstrate preferential targeting of prostate cancer stem-like cells.
- The TRAIL/DR5 pathway is implicated in NK cell-mediated elimination of prostate cancer stem cells.
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