2. Academic Validation
  3. Investigating STEAP2 as a potential therapeutic target for the treatment of aggressive prostate cancer

Investigating STEAP2 as a potential therapeutic target for the treatment of aggressive prostate cancer

  • Cell Mol Biol (Noisy-le-grand). 2023 Apr 30;69(4):179-187. doi: 10.14715/cmb/2023.69.4.28.
Leia A Jones 1,  Gillian E Conway 2,  Aimy Nguyen-Chi 3,  Stephanie Burnell 4,  Gareth J Jenkins 5,  R Steven Conlan 6,  Shareen H Doak 7
Affiliations

Affiliations

  • 1 Institute of Life Science, Swansea University Medical School, Faculty of Medicine, Health and Life Sciences, Singleton Park, Swansea, SA2 8PP, Wales, UK. Leia.Jones@cancer.org.uk.
  • 2 Institute of Life Science, Swansea University Medical School, Faculty of Medicine, Health and Life Sciences, Singleton Park, Swansea, SA2 8PP, Wales, UK. gillian.conway@swansea.ac.uk.
  • 3 Institute of Life Science, Swansea University Medical School, Faculty of Medicine, Health and Life Sciences, Singleton Park, Swansea, SA2 8PP, Wales, UK. aimy.nguyenchi@gmail.com.
  • 4 Institute of Life Science, Swansea University Medical School, Faculty of Medicine, Health and Life Sciences, Singleton Park, Swansea, SA2 8PP, Wales, UK. BurnellS@cardiff.ac.uk.
  • 5 Institute of Life Science, Swansea University Medical School, Faculty of Medicine, Health and Life Sciences, Singleton Park, Swansea, SA2 8PP, Wales, UK. G.J.Jenkins@Swansea.ac.uk.
  • 6 Institute of Life Science, Swansea University Medical School, Faculty of Medicine, Health and Life Sciences, Singleton Park, Swansea, SA2 8PP, Wales, UK. R.S.Conlan@Swansea.ac.uk.
  • 7 Institute of Life Science, Swansea University Medical School, Faculty of Medicine, Health and Life Sciences, Singleton Park, Swansea, SA2 8PP, Wales, UK. s.h.doak@swansea.ac.uk.
PMID: 37329528 DOI: 10.14715/cmb/2023.69.4.28
Abstract

The expression of six transmembrane epithelial antigen of the prostate (STEAP2) is increased in prostate Cancer when compared to normal tissue, suggesting a role for STEAP2 in disease progression. This study aimed to determine whether targeting STEAP2 with an anti-STEAP2 polyclonal antibody (pAb) or CRISPR/Cas9 knockout influenced aggressive prostate Cancer traits. Gene expression analysis of the STEAP gene family was performed in a panel of prostate Cancer cell lines; C4-2B, DU145, LNCaP and PC3. The highest increases in STEAP2 gene expression were observed in C4-2B and LNCaP cells (p<0.001 and p<0.0001 respectively) when compared to normal prostate epithelial PNT2 cells. These cell lines were treated with an anti-STEAP2 pAb and their viability assessed. CRISPR/Cas9 technology was used to knockout STEAP2 from C4-2B and LNCaP cells and viability, proliferation, migration and invasion assessed. When exposed to an anti-STEAP2 pAb, cell viability significantly decreased (p<0.05). When STEAP2 was knocked out, cell viability and proliferation was significantly decreased when compared to wild-type cells (p<0.001). The migratory and invasive potential of knockout cells were also decreased. These data suggest that STEAP2 has a functional role in driving aggressive prostate Cancer traits and could provide a novel therapeutic target for the treatment of prostate Cancer.

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