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Updated: Sep 13, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

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

Asuka Hattori1, Taiga Seki2, Kazunori Kato3

  • 1Laboratory of Molecular Bromatology, Graduate School of Sports Health, Toyo University, Tokyo, Japan.

Anticancer Research
|August 1, 2025
PubMed
Abstract

Insights

Natural killer (NK) cells show enhanced cytotoxicity against castration-resistant prostate cancer (CRPC) stem cells compared to standard CRPC cells. This suggests NK cells could be a novel therapeutic strategy for CRPC.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Stem Cell Biology

Background:

  • Castration-resistant prostate cancer (CRPC) is a lethal and treatment-refractory disease.
  • Targeting cancer stem cells is a potential strategy to eliminate CRPC, but effective methods are lacking.
  • Natural killer (NK) cells possess cytotoxic activity against cancer stem cells.

Purpose of the Study:

  • To investigate the sensitivity of CRPC cells with stemness characteristics to NK cell-mediated cytotoxicity.
  • To compare the efficacy of NK cells against CRPC stem cells versus non-stem CRPC cells.

Main Methods:

  • CRPC stem-like cells (PC3-stem) were isolated from PC-3 cells using 3D tumor sphere culture.
  • PC3-stem and PC3 cells were co-cultured with KHYG-1 NK-like cells.
  • Cell viability, mRNA levels, and protein expression were analyzed.

Main Results:

  • KHYG-1 cells demonstrated significantly greater cytotoxicity against PC3-stem cells than against PC3 cells.
  • The enhanced NK cell activity against PC3-stem cells was linked to the NKG2D-MICA/B-mediated degranulation pathway.

Conclusions:

  • NK cells exhibit preferential cytotoxicity towards CRPC stem cells.
  • Targeting CRPC stem cells with NK cells presents a promising avenue for novel therapeutic strategies against CRPC progression.
Keywords:
Castration-resistant prostate cancerMICA/BNK cellsNKG2Dcancer stem cellscytotoxicitydegranulation

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