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Updated: Jun 12, 2026
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Glioma pathogenesis-related protein 1: tumor-suppressor activities and therapeutic potential
1Department of Genitourinary Medical Oncology-Research, Unit 18-3, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA. timthomp@mdanderson.org
Abstract:
After glioma pathogenesis-related protein 1 (GLIPR1/Glipr1) was identified, the expression of GLIPR1 was shown to be down-regulated in human prostate cancer, owing in part to methylation in the regulatory region of this gene in prostate cancer cells. Additional studies showed that GLIPR1/Glipr1 expression is induced by DNA-damaging agents independent of p53. Functional analysis of GLIPR1 using in vitro and in vivo gene-transfer approaches revealed both growth suppression and proapoptotic activities for mouse Glipr1 and human GLIPR1 in multiple cancer cell lines. The proapoptotic activities were dependent on production of reactive oxygen species and sustained c-Jun-NH(2) kinase signaling. It was interesting that adenoviral vector-mediated Glipr1 (AdGlipr1) transduction into prostate cancer tissues using an immunocompetent orthotopic mouse model revealed additional biologic activities consistent with tumor-suppressor functions. Significantly reduced tumor-associated angiogenesis and direct suppression of endothelial-cell sprouting activities were documented. In addition, AdGlipr1 strongly stimulated antitumor immune responses that resulted in specific cytotoxic T-lymphocyte activities in this model. Glipr1-related antitumor immunostimulatory activities were confirmed and extended in subsequent studies. Administration of a novel Glipr1 genemodified tumor cell vaccine had significant antitumor activity in a mouse model of recurrent prostate cancer. In conclusion, restoration of GLIPR1 function in prostate cancer cells through GLIPR1 gene-based or GLIPR protein-based delivery methods may provide a safe and effective approach for targeted therapy for a range of malignancies.
Insights
Restoring glioma pathogenesis-related protein 1 (GLIPR1) function suppresses prostate cancer growth and angiogenesis. GLIPR1 gene therapy also stimulates antitumor immunity, offering a potential targeted therapy for various cancers.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Glioma pathogenesis-related protein 1 (GLIPR1) expression is reduced in prostate cancer due to gene methylation.
- GLIPR1 expression can be induced by DNA-damaging agents, independent of p53.
- GLIPR1 exhibits tumor-suppressor activities, including growth suppression and apoptosis induction.
Purpose of the Study:
- To investigate the functional roles of GLIPR1 in cancer, particularly its therapeutic potential in prostate cancer.
- To evaluate the effects of GLIPR1 restoration on tumor growth, angiogenesis, and immune responses.
Main Methods:
- In vitro and in vivo gene-transfer approaches using GLIPR1 in cancer cell lines.
- Adenoviral vector-mediated GLIPR1 (AdGlipr1) transduction in an orthotopic prostate cancer mouse model.
- Assessment of tumor-associated angiogenesis and endothelial cell sprouting.
- Evaluation of GLIPR1-induced antitumor immune responses, including cytotoxic T-lymphocyte activity.
- Testing a GLIPR1 gene-modified tumor cell vaccine in a recurrent prostate cancer model.
Main Results:
- GLIPR1 demonstrated significant growth suppression and proapoptotic activities in multiple cancer cell lines, dependent on reactive oxygen species and c-Jun-NH(2) kinase signaling.
- AdGlipr1 transduction reduced tumor-associated angiogenesis and suppressed endothelial cell sprouting.
- AdGlipr1 significantly enhanced antitumor immune responses, leading to specific cytotoxic T-lymphocyte activities.
- A GLIPR1 gene-modified tumor cell vaccine showed significant antitumor activity in a recurrent prostate cancer model.
Conclusions:
- Restoration of GLIPR1 function exhibits potent antitumor activities, including direct tumor suppression and immune stimulation.
- GLIPR1-based gene or protein delivery represents a promising strategy for targeted cancer therapy.
- This approach may be applicable to a range of malignancies beyond prostate cancer.
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