Tumor growth and metastasis suppression by Glipr1 gene-modified macrophages in a metastatic prostate cancer model

Tabata, Ken Ichi; Kurosaka, Shinji; Watanabe, Masami; Edamura, Kohei; Satoh, Takefumi; Yang, Guang; Abdelfattah, E.; Wang, Jing; Goltsov, Alexei A.; Floryk, Daniel; Thompson, Timothy C.

doi:10.1038/gt.2011.51

Cited by 11 publications

(6 citation statements)

References 34 publications

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“…Mouse Pca cell 178-2 BMA and human bladder cancer cell TSU-Pr1 were grown as described previously [9, 10, 15, 17]. All chemicals for cell culturing were from GIBCO (Gaithersburg, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

“…All chemicals for cell culturing were from GIBCO (Gaithersburg, MD, USA). AdGlipr1 (AdGLIPR1), and control Adv/CMV/βgal were prepared as described previously [9, 15]. Virus concentration was expressed as plaque-forming units (PFU).…”

Section: Methodsmentioning

confidence: 99%

“…GLIPR1, a p53 target gene, is associated with myelomonocytic differentiation toward the macrophage phenotype [9], and is shown to be methylated and downregulated in PCa [10, 11]. Functional analysis of GLIPR1 revealed both growth suppression and proapoptotic activities in multiple cancer cell lines [10-13].…”

Section: Introductionmentioning

confidence: 99%

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Combined therapeutic effects of adenoviral vector-mediated GLIPR1 gene therapy and radiotherapy in prostate and bladder cancer models

Fujita

Satoh

Timme

et al. 2014

Urologic Oncology: Seminars and Original Investigations

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Objectives To explore the potential benefits of combining AdGlipr1 (or AdGLIPR1) gene therapy with radiotherapy using subcutaneous prostate and bladder cancer models. Materials and methods Combination adenoviral vector-mediated gene therapy and radiotherapy were applied to 178-2 BMA and TSU-Pr1 cells in vitro and colony formation and apoptosis were analyzed. Also, combination therapies were administered to mice bearing subcutaneous 178-2 BMA and TSU-Pr1 tumors and tumor growth suppression and survival extension were compared with the monotherapies (AdGlipr1/ AdGLIPR1, radiotherapy) or control vector Adv/CMV/βgal as well as comparing single cycle treatment with two cycle treatment. Results Combination treatment significantly suppressed colony formation and increased apoptosis in vitro. In vivo, combination therapy produced significant 178-2 BMA and TSU-Pr1 tumor growth suppression and survival extension compared with the monotherapies or the control. Further tumor growth suppression and survival extension were observed after two cycles of the combination treatment. Conclusions Combining AdGlipr1 (AdGLIPR1) with radiotherapy may achieve additive or synergistic tumor control in selected prostate and bladder tumors, and additional therapeutic effects may result with repeated treatment cycle.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Combined therapeutic effects of adenoviral vector-mediated GLIPR1 gene therapy and radiotherapy in prostate and bladder cancer models

Fujita

Satoh

Timme

et al. 2014

Urologic Oncology: Seminars and Original Investigations

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“…Cell viability was evaluated using an MTS CellTiter 96 V R AQueous One Solution Cell Proliferation Assay (Promega, Madison, WI) according to the manufacturer's instructions as previously described. 14…”

Section: Cell Viability Assaymentioning

confidence: 99%

Systemic GLIPR1-ΔTM protein as a novel therapeutic approach for prostate cancer

et al. 2013

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GLIPR1 is a p53 target gene known to be downregulated in prostate cancer, and increased endogenous GLIPR1 expression has been associated with increased production of reactive oxygen species, increased apoptosis, decreased c-Myc protein levels, and increased cell cycle arrest. Recently, we found that upregulation of GLIPR1 in prostate cancer cells increases mitotic catastrophe through interaction with Hsc70 and downregulation of Aurora kinase A and TPX2. In the current study, we evaluated the mechanisms of recombinant GLIPR1 protein (GLIPR1-ΔTM) uptake by prostate cancer cells and the efficacy of systemic GLIPR1-ΔTM administration in a prostate cancer xenograft mouse model. GLIPR1-ΔTM was selectively internalized by prostate cancer cells, leading to increased apoptosis through reactive oxygen species production and to decreased c-Myc protein levels. Interestingly, GLIPR1-ΔTM was internalized through clathrin-mediated endocytosis in association with Hsc70. Systemic administration of GLIPR1-ΔTM significantly inhibited VCaP xenograft growth. GLIPR1-ΔTM left no evidence of toxicity after it was completely removed from the mouse models 8 hours after injection. Our results demonstrate that GLIPR1-ΔTM is selectively endocytosed by prostate cancer cells, leading to increased reactive oxygen species production and apoptosis, and that systemic GLIPR1-ΔTM significantly inhibits growth of VCaP xenografts without substantial toxicity.

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“…On a similar note, intratumoral injection of macrophage reconstructs (an adenoviral vector carrying Glipr1 gene) into an orthotopic, metastatic mouse model of PCa resulted in cancer regression. These bioengineered macrophages displayed greater surface expression of MHC class II and better production of interleukin 12 (IL-12) and IL-6 (Tabata et al 2011). …”

Section: Dna Vaccines: Well-equipped Swordsman For the Battlefieldmentioning

confidence: 99%

Prostate Cancer and Immunoproteome: Awakening and Reprogramming the Guardian Angels

Farooqı

Fayyaz

Qureshi

et al. 2012

Arch. Immunol. Ther. Exp.

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Prostate cancer is a life-threatening molecular disorder that is undruggable to date because of stumbling blocks in the standardization of therapy. An emerging framework of research is addressing how pathways that are derailed during tumorigenesis are linked to immunological responses, which are instrumental in immunosurveillance of cancer. However, interestingly, cancer cells circumvent such immunosurveillance through development of poorly immunogenic tumor cell variants (immunoselection) and through subversion of the immunological nanomachinery (immunosubversion). Detailed mechanistic insights of molecular specificities that regulate natural killer (NK) cell function suggest that it might be promising to design NK cell-based immunotherapeutic interventions against prostate cancer. Here, we elucidate evidence for NK cell targeting of prostate cancer proteome and address critical questions that, in our view, need thoughtfulness for the development of successful NK cell-based therapies. This review also disproves our contemporary understanding of the versatile regulators of DNA damage repair (ATM, ATR) that trigger cell surface expression of NKG2D ligands and consequent elimination of the tumor cells by NK cells and other lymphocytes that express NK cell receptors. Substantial fraction of information has been generated that guarantees productive future for this technology as more optimized constructs, better trial designs, and improved platforms are being brought from benchtop to bedside.

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Tumor growth and metastasis suppression by Glipr1 gene-modified macrophages in a metastatic prostate cancer model

Cited by 11 publications

References 34 publications

Combined therapeutic effects of adenoviral vector-mediated GLIPR1 gene therapy and radiotherapy in prostate and bladder cancer models

Combined therapeutic effects of adenoviral vector-mediated GLIPR1 gene therapy and radiotherapy in prostate and bladder cancer models

Systemic GLIPR1-ΔTM protein as a novel therapeutic approach for prostate cancer

Prostate Cancer and Immunoproteome: Awakening and Reprogramming the Guardian Angels

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