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Immunology

Abstract #1251: CXCL12 and its receptors CXCR4 and CXCR7 as potential molecular targets for lung cancer

Hisao Imai, Noriaki Sunaga, Yasuo Shimizu, Noriko Yanagitani, Kyoichi Kaira, Yoshio Tomizawa, Tamotsu Ishizuka, Ryusei Saito, John Minna and Masatomo Mori
Hisao Imai
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan; Department of Respiratory Medicine, National Nishigunma Hospital, Gunma, Japan; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
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Noriaki Sunaga
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan; Department of Respiratory Medicine, National Nishigunma Hospital, Gunma, Japan; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
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Yasuo Shimizu
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan; Department of Respiratory Medicine, National Nishigunma Hospital, Gunma, Japan; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
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Noriko Yanagitani
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan; Department of Respiratory Medicine, National Nishigunma Hospital, Gunma, Japan; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
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Kyoichi Kaira
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan; Department of Respiratory Medicine, National Nishigunma Hospital, Gunma, Japan; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
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Yoshio Tomizawa
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan; Department of Respiratory Medicine, National Nishigunma Hospital, Gunma, Japan; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
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Tamotsu Ishizuka
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan; Department of Respiratory Medicine, National Nishigunma Hospital, Gunma, Japan; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
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Ryusei Saito
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan; Department of Respiratory Medicine, National Nishigunma Hospital, Gunma, Japan; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
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John Minna
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan; Department of Respiratory Medicine, National Nishigunma Hospital, Gunma, Japan; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
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Masatomo Mori
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan; Department of Respiratory Medicine, National Nishigunma Hospital, Gunma, Japan; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
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DOI:  Published May 2009
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AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Abstract

The interaction between the chemokine CXCL12 and the two receptors, CXCR4 and CXCR7, is thought to play a role in tumor growth and metastasis in human cancers. However, the expression of CXCL12, CXCR4 and CXCR7 and their role in lung cancer is not fully elucidated. Here we examined the expression of CXCL12, CXCR4 and CXCR7 in 23 small cell lung cancer (SCLC) cell lines and 32 non-small cell lung cancer (NSCLC) cell lines. CXCL12, CXCR4 and CXCR7 were overexpressed in lung cancer cell lines compared with human non-malignant lung epithelial cells (N=6). CXCR4 levels were significantly higher in SCLCs than those in NSCLCs, while there were no differences in the levels of both CXCL12 and CXCR7 between SCLCs and NSCLCs. Frequencies of CXCL12, CXCR4 and CXCR7 overexpression were 45%, 80% and 16%, respectively, and CXCL12 expression was positively associated with expression of CXCR4 and CXCR7. RNA interference-mediated CXCL12 knockdown inhibited cell growth and migration in a CXCL12-overexpressing lung cancer cells, and the effect involved inactivation of the MEK-ERK pathway. Furthermore, treatment with an anti-CXCL12 neutralizing antibody inhibited cell growth in four of CXCL12-overexpressing lung cancer cell lines but not in CXCL12 non-expressing lines. The results demonstrate that: CXCL12, CXCR4 and CXCR7 are concomitantly overexpressed in lung cancers; CXCR4 is abundantly expressed in SCLCs compared with NSCLCs; and that CXCL12 is required for lung cancer cell growth and migration via the MEK-ERK signaling pathway. Thus, inhibition of CXCL12 activity could be a novel therapeutic approach in lung cancer.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1251.

Footnotes

  • 100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

  • American Association for Cancer Research
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Cancer Research: 69 (9 Supplement)
May 2009
Volume 69, Issue 9 Supplement
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Abstract #1251: CXCL12 and its receptors CXCR4 and CXCR7 as potential molecular targets for lung cancer
Hisao Imai, Noriaki Sunaga, Yasuo Shimizu, Noriko Yanagitani, Kyoichi Kaira, Yoshio Tomizawa, Tamotsu Ishizuka, Ryusei Saito, John Minna and Masatomo Mori
Cancer Res May 1 2009 (69) (9 Supplement) 1251;

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Abstract #1251: CXCL12 and its receptors CXCR4 and CXCR7 as potential molecular targets for lung cancer
Hisao Imai, Noriaki Sunaga, Yasuo Shimizu, Noriko Yanagitani, Kyoichi Kaira, Yoshio Tomizawa, Tamotsu Ishizuka, Ryusei Saito, John Minna and Masatomo Mori
Cancer Res May 1 2009 (69) (9 Supplement) 1251;
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