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A novel therapeutic strategy with anti-CD9 antibody in gastric cancers

  • Original Article—Alimentary Tract
  • Published:
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Abstract

Background

CD9 is a member of the tetraspanins, and has been shown to be involved in a variety of cellular activities such as motility, cell signaling, proliferation, adhesion, and metastasis. However, very little is known about the involvement of CD9 in the process of development of primary tumors. In the present study, we investigated whether anti-CD9 monoclonal antibody (ALB6) has antitumor effects in human gastric cancer cell xenografts.

Methods

Human gastric cancer cell lines (MKN-28) (5 × 106 cells/animal) were inoculated subcutaneously into the dorsal region of SCID mice (five mice in each group). After a tumor was visualized, animals were assigned to either the ALB6 treatment group or the control IgG treatment group (100 μg/body/time, intravenous, three times per week. Day 1, 4, and 7 of first week). Then tumor volumes were monitored every day. Proliferation of tumor was analyzed by 5-bromo-2′-deoxyuridine (BrdU) immunostaining, apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) methods, and angiogenesis was assessed by counting the number of CD34-positive endothelial cells.

Results

Tumor volume was significantly suppressed (1,682 ± 683 mm3 versus 4,507 ± 1,012 mm3; P = 0.049), the BrdU labeling indexes were significantly decreased (10.9 ± 1.1% versus 17.2 ± 1.4%; P = 0.009), the apoptotic indexes were significantly increased (1.98 ± 0.48% versus 0.72 ± 0.09%; P = 0.034), and tumor microvessel densities were significantly suppressed (671,922 ± 34,505 pixels/mm2 versus 1,135,043 ± 36,086 pixels/mm2; P = 0.037) in the ALB6 treatment group compared with the control IgG treatment group.

Conclusions

These results suggest that administration of anti-CD9 antibody to mice bearing human gastric cancer cells successfully inhibits tumor progression via antiproliferative, proapoptotic, and antiangiogenetic effects.

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Abbreviations

BrdU:

5-Bromo-2′-deoxyuridine

JNK/SAPK:

c-Jun NH2-terminal kinase/stress-activated protein kinase

MAPK:

Mitogen-activated-protein kinase

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling

ABC:

Avidin–biotin peroxidase complex

DAB:

3,3′-Diaminobenzidine tetrahydrochloride

FCS:

Fetal calf serum

PBS:

Phosphate-buffered saline

EGFR:

Epidermal growth factor receptor

SEM:

Standard error of the mean

cDNA:

complementary Deoxyribonucleic acid

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Acknowledgments

This work was supported in part by grants-in-aid (grant 10359846 to S. Tsutsui) from the Ministry of Education, Science, Sports, and Culture of Japan.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Japan

    Taisei Nakamoto, Kenji Watabe, Shinichi Kiso, Shusaku Tsutsui & Norio Hayashi

  2. Department of Gastroenterology and Hepatology, Itami City Hospital, Koyaike 1-100, Itami, Japan

    Yoko Murayama

  3. Department of Hematology/Oncology, Graduate School of Medicine, Osaka University, Suita, Japan

    Kenji Oritani

  4. Institut National de la Santé et de la Recherche Medicale, Unité 554, Montpellier, France

    Claude Boucheix & Eric Rubinstein

  5. Health Care Center, Osaka University, Toyonaka, Japan

    Makoto Nishida

  6. Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan

    Fumie Katsube

  7. Department of Internal Medicine, Minoh City Hospital, Minoh, Japan

    Shinji Tamura

  8. First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan

    Yasuhisa Shinomura

Authors
  1. Taisei Nakamoto
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  2. Yoko Murayama
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  4. Claude Boucheix
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  9. Shinichi Kiso
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  10. Shusaku Tsutsui
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  12. Yasuhisa Shinomura
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  13. Norio Hayashi
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Corresponding author

Correspondence to Yoko Murayama.

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Nakamoto, T., Murayama, Y., Oritani, K. et al. A novel therapeutic strategy with anti-CD9 antibody in gastric cancers. J Gastroenterol 44, 889–896 (2009). https://doi.org/10.1007/s00535-009-0081-3

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  • DOI: https://doi.org/10.1007/s00535-009-0081-3

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