Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma

J. Yamamoto, K. Ohnuma, R. Hatano, T. Okamoto, E. Komiya, H. Yamazaki, S. Iwata, N. H. Dang, K. Aoe, T. Kishimoto, T. Yamada, C. Morimoto

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm arising from mesothelial lining of pleura. CD26 molecules preferentially expressed on epithelioid type of MPM. This study investigates the molecular mechanisms of CD26 regulating MPM cells in vitro and in vivo. Methods: Biochemical and cell biological approaches were used for identifying a novel molecular target of MPM. Its contribution to tumour expansion has been also assessed using animal models. The clinical samples of MPM were also assessed for its expression. Results: We identify that cytostatic effects in MPM are mediated by somatostatin (SST) receptor 4 (SSTR4), being inhibited by the interaction of CD26 molecules. We also indicates that SSTR4-mediated cytostatic effects are regulated by SHP-2 PTP, and that this inhibitory effect by SST agonist is enhanced via lipid raft clustering of associated molecules following crosslinking of anti-CD26 antibody. Finally, using an in vivo xenograft model, we demonstrate that the anti-tumour effect of anti-CD26 mAb is enhanced when combined with SSTR4 agonist treatment, and that SSTR4 is highly coexpressed with CD26 on epithelioid or biphasic types of MPM tissues obtained from patients' surgical specimens. Conclusions: Combination therapy with humanised anti-CD26 mAb and SSTR4 agonist may therefore potentiate anti-tumour effect on MPM.

Original languageEnglish
Pages (from-to)2232-2245
Number of pages14
JournalBritish Journal of Cancer
Volume110
Issue number9
DOIs
Publication statusPublished - 2014 Apr 29

Fingerprint

Cytostatic Agents
Mesothelial Neoplasms
Neoplasms
Malignant Mesothelioma
somatostatin receptor subtype-4
Pleura
Somatostatin
Heterografts
Cluster Analysis
Anti-Idiotypic Antibodies
Animal Models
Lipids
Therapeutics

Keywords

  • CD26
  • malignant pleural mesothelioma
  • SHP-2
  • somatostatin
  • SSTR4

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Yamamoto, J., Ohnuma, K., Hatano, R., Okamoto, T., Komiya, E., Yamazaki, H., ... Morimoto, C. (2014). Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma. British Journal of Cancer, 110(9), 2232-2245. https://doi.org/10.1038/bjc.2014.151

Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma. / Yamamoto, J.; Ohnuma, K.; Hatano, R.; Okamoto, T.; Komiya, E.; Yamazaki, H.; Iwata, S.; Dang, N. H.; Aoe, K.; Kishimoto, T.; Yamada, T.; Morimoto, C.

In: British Journal of Cancer, Vol. 110, No. 9, 29.04.2014, p. 2232-2245.

Research output: Contribution to journalArticle

Yamamoto, J, Ohnuma, K, Hatano, R, Okamoto, T, Komiya, E, Yamazaki, H, Iwata, S, Dang, NH, Aoe, K, Kishimoto, T, Yamada, T & Morimoto, C 2014, 'Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma', British Journal of Cancer, vol. 110, no. 9, pp. 2232-2245. https://doi.org/10.1038/bjc.2014.151
Yamamoto, J. ; Ohnuma, K. ; Hatano, R. ; Okamoto, T. ; Komiya, E. ; Yamazaki, H. ; Iwata, S. ; Dang, N. H. ; Aoe, K. ; Kishimoto, T. ; Yamada, T. ; Morimoto, C. / Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma. In: British Journal of Cancer. 2014 ; Vol. 110, No. 9. pp. 2232-2245.
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