NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients with lung cancer

Koichi Azuma, Akihiko Kawahara, Satoshi Hattori, Tomoki Taira, Junji Tsurutani, Kosuke Watari, Tomohiro Shibata, Yuichi Murakami, Shinzo Takamori, Mayumi Ono, Hiroto Izumi, Masayoshi Kage, Takashi Yanagawa, Kazuhiko Nakagawa, Tomoaki Hoshino, Michihiko Kuwano

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Objective: Expression of N-myc downstream-regulated gene 1 (NDRG1)/Cap43 is a prognostic indicator of human malignancies according to the tumor type in which it occurs. We investigated how NDRG1/Cap43 could affect tumor growth and angiogenesis in non-small-cell lung cancer (NSCLC) in vivo using an animal experimental model, and also how it could affect tumor angiogenesis and prognosis in NSCLC patients. Methods and Results: Knockdown of NDRG1/Cap43 in lung cancer cells using a specific small interfering RNA resulted in growth rates in culture that were similar to those of counterpart control cells, but decreased tumor growth rates in vivo markedly. Stable NDRG1/Cap43 knockdown did not induce consistent changes in the expression of Epidermal growth factor receptor (EGFR) family proteins and c-Met in two human lung cancer cell lines in vitro. However, cell lines with NDRG1/Cap43 knockdown showed markedly decreased production of the potent angiogenic factors vascular endothelial growth factor-A and interleukin-8. Cells with knockdown of NDRG1/Cap43 showed marked reduction of tumor-induced angiogenesis. Using immunohistochemistry, we examined 182 surgically resected specimens of NSCLC for expression of NDRG1/Cap43 and tumor angiogenesis. High microvessel density in the tumor was significantly associated with nuclear positivity for NDRG1/Cap43 in both adenocarcinoma (p = 0.003) and squamous cell carcinoma (p=0.041). For both adenocarcinoma (p = 0.031) and squamous cell carcinoma (p=0.034), the survival curve of patients negative for nuclear NDRG1/Cap43 expression differed significantly from that of patients who were positive. Conclusion: Therefore, the expression of NDRG1/Cap43 may be predictive of tumor angiogenesis and poor prognosis in NSCLC.

Original languageEnglish
Pages (from-to)779-789
Number of pages11
JournalJournal of Thoracic Oncology
Volume7
Issue number5
DOIs
Publication statusPublished - Jan 1 2012

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Lung Neoplasms
Genes
Neoplasms
Non-Small Cell Lung Carcinoma
Squamous Cell Carcinoma
Adenocarcinoma
Growth
Cell Line
Angiogenesis Inducing Agents
Microvessels
Interleukin-8
Vascular Endothelial Growth Factor A
Small Interfering RNA
Animal Models
Immunohistochemistry
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients with lung cancer. / Azuma, Koichi; Kawahara, Akihiko; Hattori, Satoshi; Taira, Tomoki; Tsurutani, Junji; Watari, Kosuke; Shibata, Tomohiro; Murakami, Yuichi; Takamori, Shinzo; Ono, Mayumi; Izumi, Hiroto; Kage, Masayoshi; Yanagawa, Takashi; Nakagawa, Kazuhiko; Hoshino, Tomoaki; Kuwano, Michihiko.

In: Journal of Thoracic Oncology, Vol. 7, No. 5, 01.01.2012, p. 779-789.

Research output: Contribution to journalArticle

Azuma, K, Kawahara, A, Hattori, S, Taira, T, Tsurutani, J, Watari, K, Shibata, T, Murakami, Y, Takamori, S, Ono, M, Izumi, H, Kage, M, Yanagawa, T, Nakagawa, K, Hoshino, T & Kuwano, M 2012, 'NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients with lung cancer', Journal of Thoracic Oncology, vol. 7, no. 5, pp. 779-789. https://doi.org/10.1097/JTO.0b013e31824c92b4
Azuma, Koichi ; Kawahara, Akihiko ; Hattori, Satoshi ; Taira, Tomoki ; Tsurutani, Junji ; Watari, Kosuke ; Shibata, Tomohiro ; Murakami, Yuichi ; Takamori, Shinzo ; Ono, Mayumi ; Izumi, Hiroto ; Kage, Masayoshi ; Yanagawa, Takashi ; Nakagawa, Kazuhiko ; Hoshino, Tomoaki ; Kuwano, Michihiko. / NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients with lung cancer. In: Journal of Thoracic Oncology. 2012 ; Vol. 7, No. 5. pp. 779-789.
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T1 - NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients with lung cancer

AU - Azuma, Koichi

AU - Kawahara, Akihiko

AU - Hattori, Satoshi

AU - Taira, Tomoki

AU - Tsurutani, Junji

AU - Watari, Kosuke

AU - Shibata, Tomohiro

AU - Murakami, Yuichi

AU - Takamori, Shinzo

AU - Ono, Mayumi

AU - Izumi, Hiroto

AU - Kage, Masayoshi

AU - Yanagawa, Takashi

AU - Nakagawa, Kazuhiko

AU - Hoshino, Tomoaki

AU - Kuwano, Michihiko

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Objective: Expression of N-myc downstream-regulated gene 1 (NDRG1)/Cap43 is a prognostic indicator of human malignancies according to the tumor type in which it occurs. We investigated how NDRG1/Cap43 could affect tumor growth and angiogenesis in non-small-cell lung cancer (NSCLC) in vivo using an animal experimental model, and also how it could affect tumor angiogenesis and prognosis in NSCLC patients. Methods and Results: Knockdown of NDRG1/Cap43 in lung cancer cells using a specific small interfering RNA resulted in growth rates in culture that were similar to those of counterpart control cells, but decreased tumor growth rates in vivo markedly. Stable NDRG1/Cap43 knockdown did not induce consistent changes in the expression of Epidermal growth factor receptor (EGFR) family proteins and c-Met in two human lung cancer cell lines in vitro. However, cell lines with NDRG1/Cap43 knockdown showed markedly decreased production of the potent angiogenic factors vascular endothelial growth factor-A and interleukin-8. Cells with knockdown of NDRG1/Cap43 showed marked reduction of tumor-induced angiogenesis. Using immunohistochemistry, we examined 182 surgically resected specimens of NSCLC for expression of NDRG1/Cap43 and tumor angiogenesis. High microvessel density in the tumor was significantly associated with nuclear positivity for NDRG1/Cap43 in both adenocarcinoma (p = 0.003) and squamous cell carcinoma (p=0.041). For both adenocarcinoma (p = 0.031) and squamous cell carcinoma (p=0.034), the survival curve of patients negative for nuclear NDRG1/Cap43 expression differed significantly from that of patients who were positive. Conclusion: Therefore, the expression of NDRG1/Cap43 may be predictive of tumor angiogenesis and poor prognosis in NSCLC.

AB - Objective: Expression of N-myc downstream-regulated gene 1 (NDRG1)/Cap43 is a prognostic indicator of human malignancies according to the tumor type in which it occurs. We investigated how NDRG1/Cap43 could affect tumor growth and angiogenesis in non-small-cell lung cancer (NSCLC) in vivo using an animal experimental model, and also how it could affect tumor angiogenesis and prognosis in NSCLC patients. Methods and Results: Knockdown of NDRG1/Cap43 in lung cancer cells using a specific small interfering RNA resulted in growth rates in culture that were similar to those of counterpart control cells, but decreased tumor growth rates in vivo markedly. Stable NDRG1/Cap43 knockdown did not induce consistent changes in the expression of Epidermal growth factor receptor (EGFR) family proteins and c-Met in two human lung cancer cell lines in vitro. However, cell lines with NDRG1/Cap43 knockdown showed markedly decreased production of the potent angiogenic factors vascular endothelial growth factor-A and interleukin-8. Cells with knockdown of NDRG1/Cap43 showed marked reduction of tumor-induced angiogenesis. Using immunohistochemistry, we examined 182 surgically resected specimens of NSCLC for expression of NDRG1/Cap43 and tumor angiogenesis. High microvessel density in the tumor was significantly associated with nuclear positivity for NDRG1/Cap43 in both adenocarcinoma (p = 0.003) and squamous cell carcinoma (p=0.041). For both adenocarcinoma (p = 0.031) and squamous cell carcinoma (p=0.034), the survival curve of patients negative for nuclear NDRG1/Cap43 expression differed significantly from that of patients who were positive. Conclusion: Therefore, the expression of NDRG1/Cap43 may be predictive of tumor angiogenesis and poor prognosis in NSCLC.

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