Related Experiment Video
Updated: Jun 2, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Tumor growth and metastasis suppression by Glipr1 gene-modified macrophages in a metastatic prostate cancer model
K Tabata1, S Kurosaka, M Watanabe
1Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA.
Abstract:
We previously identified the mouse and human Glipr1 and GLIPR1/RTVP-1 genes, respectively, as direct p53 targets with proapoptotic activities in various cancer cell lines, including prostate cancer (PCa). Intratumoral injection of an adenoviral vector capable of efficient transduction and expression of Glipr1 (AdGlipr1) yielded promising therapeutic results in an orthotopic, metastatic mouse model of PCa. AdGlipr1-transduced macrophages (Mφ/Glipr1) generated greater surface expression of CD40, CD80 and major histocompatibility complex class II molecules and greater production of interleukin 12 (IL-12) and IL-6 in vitro than control macrophages did. Mechanistic analysis indicated that increased production of IL-12 in Mφ/Glipr1 depends on activation of the p38 signaling cascade. Mφ/Glipr1 injected into orthotopic 178-2BMA tumors in vivo resulted in significantly suppressed prostate tumor growth and spontaneous lung metastases and longer survival relative to those observed in control-treated mice. Furthermore, these preclinical data indicate the generation of systemic natural killer cell activity and tumor-specific cytotoxic T lymphocyte responses. Trafficking studies confirmed that intratumorally injected Mφ/Glipr1 could migrate to draining lymph nodes. Overall, our data suggest that this novel gene-modified cell approach is an effective treatment avenue that induces antitumor immune responses in preclinical studies.
Insights
Gene-modified macrophages expressing Glipr1 suppressed prostate tumor growth and metastasis in mice. This novel cell therapy approach activated antitumor immune responses, offering a promising new avenue for cancer treatment.
Area of Science:
- Oncology
- Immunology
- Gene Therapy
Background:
- The Glipr1 gene was identified as a direct p53 target with proapoptotic activity in cancer cells, including prostate cancer.
- Previous studies showed promising therapeutic results using an adenoviral vector expressing Glipr1 (AdGlipr1) in a mouse model of prostate cancer.
Purpose of the Study:
- To evaluate the efficacy of Glipr1-transduced macrophages (Mφ/Glipr1) as a novel cell-based therapy for prostate cancer.
- To investigate the immune-modulating effects and antitumor mechanisms of Mφ/Glipr1 in preclinical models.
Main Methods:
- Macrophages were transduced with AdGlipr1 (Mφ/Glipr1) and characterized for surface marker expression and cytokine production (IL-12, IL-6).
- Mechanistic studies explored the role of the p38 signaling cascade in IL-12 production.
- Mφ/Glipr1 were injected into orthotopic prostate tumors in mice to assess tumor growth, metastasis, survival, and immune responses (NK cells, CTLs).
- Trafficking of injected Mφ/Glipr1 to draining lymph nodes was confirmed.
Main Results:
- Mφ/Glipr1 exhibited enhanced expression of CD40, CD80, and MHC class II, along with increased IL-12 and IL-6 production, dependent on p38 activation.
- Intratumoral injection of Mφ/Glipr1 significantly suppressed prostate tumor growth and lung metastases, leading to prolonged survival in mice.
- Systemic natural killer cell activity and tumor-specific cytotoxic T lymphocyte responses were induced.
- Injected Mφ/Glipr1 demonstrated migration to draining lymph nodes.
Conclusions:
- Glipr1-modified macrophages represent a novel and effective cell-based therapy for prostate cancer.
- This approach induces potent antitumor immune responses, including enhanced antigen presentation and T cell activation.
- The findings support the potential of gene-modified cell therapy for treating metastatic prostate cancer.
