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Updated: Jan 22, 2026
Intra-Cardiac Injection of Human Prostate Cancer Cells to Create a Bone Metastasis Xenograft Mouse Model
Published on: November 4, 2022
GPRC5A facilitates cell proliferation through cell cycle regulation and correlates with bone metastasis in prostate
Yuichiro Sawada1,2,3, Tadahiko Kikugawa1, Hiroyuki Iio1,2,3
1Department of Urology, Ehime University Graduate School of Medicine, Toon, Japan.
Abstract:
The prognosis of patients with progressive prostate cancers that are hormone refractory and/or have bone metastasis is poor. Multiple therapeutic targets to improve prostate cancer patient survival have been investigated, including orphan GPCRs. In our study, we identified G Protein-Coupled Receptor Class C Group 5 Member A (GPRC5A) as a candidate therapeutic molecule using integrative gene expression analyses of registered data sets for prostate cancer cell lines. Kaplan-Meier analysis of TCGA data sets revealed that patients who have high GPRC5A expression had significantly shorter overall survival. PC3 prostate cancer cells with CRISPR/Cas9-mediated GPRC5A knockout exhibited significantly reduced cell proliferation both in vitro and in vivo. RNA-seq revealed that GPRC5A KO PC3 cells had dysregulated expression of cell cycle-related genes, leading to cell cycle arrest at the G2/M phase. Furthermore, the registered gene expression profile data set showed that the expression level of GPRC5A in original lesions of prostate cancer patients with bone metastasis was higher than that without bone metastasis. In fact, GPRC5A KO PC3 cells failed to establish bone metastasis in xenograft mice models. In addition, our clinical study revealed that GPRC5A expression levels in prostate cancer patient samples were significantly correlated with bone metastasis as well as the patient's Gleason score (GS). Combined assessment with the immunoreactivity of GPRC5A and GS displayed higher specificity for predicting the occurrence of bone metastasis. Together, our findings indicate that GPRC5A can be a possible therapeutic target and prognostic marker molecule for progressive prostate cancer.
Insights
G Protein-Coupled Receptor Class C Group 5 Member A (GPRC5A) is a potential therapeutic target for progressive prostate cancer. High GPRC5A expression correlates with shorter survival and bone metastasis, suggesting its role in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prognosis for hormone-refractory prostate cancer with bone metastasis is poor.
- Orphan G protein-coupled receptors (GPCRs) are investigated as therapeutic targets.
- GPRC5A emerged as a candidate molecule from gene expression analysis.
Purpose of the Study:
- To investigate the role of GPRC5A in prostate cancer progression.
- To evaluate GPRC5A as a potential therapeutic target and prognostic marker.
Main Methods:
- Integrative gene expression analysis of prostate cancer datasets.
- Kaplan-Meier survival analysis using TCGA data.
- CRISPR/Cas9-mediated GPRC5A knockout in PC3 cells.
- RNA-sequencing (RNA-seq) for gene expression profiling.
- Xenograft mouse models for in vivo studies.
- Clinical sample analysis correlating GPRC5A with metastasis and Gleason score.
Main Results:
- High GPRC5A expression is linked to significantly shorter overall survival.
- GPRC5A knockout reduced prostate cancer cell proliferation in vitro and in vivo.
- GPRC5A knockout led to cell cycle arrest at the G2/M phase.
- GPRC5A expression is higher in primary lesions of patients with bone metastasis.
- GPRC5A knockout cells failed to establish bone metastasis in xenograft models.
- Clinical samples showed GPRC5A levels correlate with bone metastasis and Gleason score.
Conclusions:
- GPRC5A is implicated in prostate cancer progression, proliferation, and metastasis.
- GPRC5A serves as a potential prognostic marker for bone metastasis.
- GPRC5A represents a promising therapeutic target for progressive prostate cancer.
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