Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model

K. Edamura; Y. Nasu; M. Takaishi; T. Kobayashi; F. Abarzua; M. Sakaguchi; Y. Kashiwakura; Shin Ebara; T. Saika; M. Watanabe; N. H. Huh; H. Kumon

doi:10.1038/sj.cgt.7701071

Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model

K. Edamura, Y. Nasu, M. Takaishi, T. Kobayashi, F. Abarzua, M. Sakaguchi, Y. Kashiwakura, Shin Ebara, T. Saika, M. Watanabe, N. H. Huh, H. Kumon

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59 Citations (Scopus)

Abstract

We had previously reported that REIC/Dkk-3, a member of the Dickkopf (Dkk) gene family, works as a tumor suppressor. In this study, we evaluated the therapeutic effects of an intratumoral injection with adenoviral vector encoding REIC/Dkk-3 gene (Ad-REIC) using an orthotopic mouse prostate cancer model of RM-9 cells. We also investigated the in vivo anti-metastatic effect and in vitro anti-invasion effect of Ad-REIC gene delivery. We demonstrated that the Ad-REIC treatment inhibited prostate cancer growth and lymph node metastasis, and prolonged mice survival in the model. These therapeutic responses were consistent with the intratumoral apoptosis induction and in vitro suppression of cell invasion/migration with reduced matrix metalloprotease-2 activity. We thus concluded that in situ Ad-REIC/Dkk-3 gene transfer may be a promising therapeutic intervention modality for the treatment of prostate cancer.

Original language	English
Pages (from-to)	765-772
Number of pages	8
Journal	Cancer Gene Therapy
Volume	14
Issue number	9
DOIs	https://doi.org/10.1038/sj.cgt.7701071
Publication status	Published - 2007

Keywords

Apoptosis
Dkk-3
Invasion
Metastasis
Prostate cancer
REIC

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model",

abstract = "We had previously reported that REIC/Dkk-3, a member of the Dickkopf (Dkk) gene family, works as a tumor suppressor. In this study, we evaluated the therapeutic effects of an intratumoral injection with adenoviral vector encoding REIC/Dkk-3 gene (Ad-REIC) using an orthotopic mouse prostate cancer model of RM-9 cells. We also investigated the in vivo anti-metastatic effect and in vitro anti-invasion effect of Ad-REIC gene delivery. We demonstrated that the Ad-REIC treatment inhibited prostate cancer growth and lymph node metastasis, and prolonged mice survival in the model. These therapeutic responses were consistent with the intratumoral apoptosis induction and in vitro suppression of cell invasion/migration with reduced matrix metalloprotease-2 activity. We thus concluded that in situ Ad-REIC/Dkk-3 gene transfer may be a promising therapeutic intervention modality for the treatment of prostate cancer.",

keywords = "Apoptosis, Dkk-3, Invasion, Metastasis, Prostate cancer, REIC",

author = "K. Edamura and Y. Nasu and M. Takaishi and T. Kobayashi and F. Abarzua and M. Sakaguchi and Y. Kashiwakura and Shin Ebara and T. Saika and M. Watanabe and Huh, {N. H.} and H. Kumon",

note = "Funding Information: This work was supported by a Scientific Research Grant from the Japan Society for the Promotion of Science (B(2) 15390491; Y Nasu) and a Health and Labor Sciences Research Grant from the Ministry of Health, Labor and Welfare (Third Term Comprehensive Control Research for Cancer; H Kumon). We thank Genofunction, Co. Ltd for providing an adenovirus vector carrying REIC/Dkk-3, and Yuka Matono and Katsuo Ohno for their technical assistance.",

year = "2007",

doi = "10.1038/sj.cgt.7701071",

language = "English",

volume = "14",

pages = "765--772",

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T1 - Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model

AU - Edamura, K.

AU - Nasu, Y.

AU - Takaishi, M.

AU - Kobayashi, T.

AU - Abarzua, F.

AU - Sakaguchi, M.

AU - Kashiwakura, Y.

AU - Ebara, Shin

AU - Saika, T.

AU - Watanabe, M.

AU - Huh, N. H.

AU - Kumon, H.

N1 - Funding Information: This work was supported by a Scientific Research Grant from the Japan Society for the Promotion of Science (B(2) 15390491; Y Nasu) and a Health and Labor Sciences Research Grant from the Ministry of Health, Labor and Welfare (Third Term Comprehensive Control Research for Cancer; H Kumon). We thank Genofunction, Co. Ltd for providing an adenovirus vector carrying REIC/Dkk-3, and Yuka Matono and Katsuo Ohno for their technical assistance.

PY - 2007

Y1 - 2007

N2 - We had previously reported that REIC/Dkk-3, a member of the Dickkopf (Dkk) gene family, works as a tumor suppressor. In this study, we evaluated the therapeutic effects of an intratumoral injection with adenoviral vector encoding REIC/Dkk-3 gene (Ad-REIC) using an orthotopic mouse prostate cancer model of RM-9 cells. We also investigated the in vivo anti-metastatic effect and in vitro anti-invasion effect of Ad-REIC gene delivery. We demonstrated that the Ad-REIC treatment inhibited prostate cancer growth and lymph node metastasis, and prolonged mice survival in the model. These therapeutic responses were consistent with the intratumoral apoptosis induction and in vitro suppression of cell invasion/migration with reduced matrix metalloprotease-2 activity. We thus concluded that in situ Ad-REIC/Dkk-3 gene transfer may be a promising therapeutic intervention modality for the treatment of prostate cancer.

AB - We had previously reported that REIC/Dkk-3, a member of the Dickkopf (Dkk) gene family, works as a tumor suppressor. In this study, we evaluated the therapeutic effects of an intratumoral injection with adenoviral vector encoding REIC/Dkk-3 gene (Ad-REIC) using an orthotopic mouse prostate cancer model of RM-9 cells. We also investigated the in vivo anti-metastatic effect and in vitro anti-invasion effect of Ad-REIC gene delivery. We demonstrated that the Ad-REIC treatment inhibited prostate cancer growth and lymph node metastasis, and prolonged mice survival in the model. These therapeutic responses were consistent with the intratumoral apoptosis induction and in vitro suppression of cell invasion/migration with reduced matrix metalloprotease-2 activity. We thus concluded that in situ Ad-REIC/Dkk-3 gene transfer may be a promising therapeutic intervention modality for the treatment of prostate cancer.

KW - Apoptosis

KW - Dkk-3

KW - Invasion

KW - Metastasis

KW - Prostate cancer

KW - REIC

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Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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