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Glycosylation of ascites-derived exosomal CD133: a potential prognostic biomarker in patients with advanced pancreatic cancer

  • Takahiko Sakaue
  • Hironori KogaEmail author
  • Hideki Iwamoto
  • Toru Nakamura
  • Yu Ikezono
  • Mitsuhiko Abe
  • Fumitaka Wada
  • Atsutaka Masuda
  • Toshimitsu Tanaka
  • Masaru Fukahori
  • Tomoyuki Ushijima
  • Yuutarou Mihara
  • Yoshiki Naitou
  • Yoshinobu Okabe
  • Tatsuyuki Kakuma
  • Keisuke Ohta
  • Kei-ichiro Nakamura
  • Takuji Torimura
Original Paper

Abstract

Cancer cells surviving in ascites exhibit cancer stem cell (CSC)-like features. This study analyzed the expression of the CSC marker CD133 in the ascites-derived exosomes obtained from patients with unresectable pancreatic cancer. In addition, inverse correlation of CD133 expression with prognosis was examined. Of the 133 consecutive patients, 19 patients were enrolled in the study. Exosomes derived from the malignant ascites demonstrated higher density and wider variation in size than those from non-malignant ascites. Western blot revealed enhanced expression of CD133 in exosomes obtained from patients with pancreatic cancer compared to those obtained from patients with gastric cancer or liver cirrhosis. A xenograft mouse model with malignant ascites was established by intraperitoneal inoculation of human pancreatic cancer cells in nude mice. Results obtained from the human study were reproduced in the mouse model. Statistically significant equilateral correlation was identified between the band intensity of CD133 in western blot and overall survival of patients. Lectin microarray analyses revealed glycosylation of CD133 by sialic acids as the major glycosylation among diverse others responsible for the glycosylation of exosomal CD133. These findings suggest that highly glycosylated CD133 in ascites-derived exosomes as a potential biomarker for better prognosis of patients with advanced pancreatic cancer.

Keywords

Pancreatic cancer Exosome Ascites CD133 Glycosylation Prognostic biomarker 

Notes

Acknowledgements

We thank Ryuhei Higashi, Yasuko Imamura, and Masako Hayakawa for their able technical assistance. We would like to thank Editage for editing and reviewing this manuscript for English language.

Funding

This work was supported by The Promotion and Mutual Aid Corporation for Private Schools of Japan (PMAC) Scholarship Fund for Young Researchers.

Compliance with ethical standards

Conflict of interest

The authors have no potential conflicts of interest to be disclosed.

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Copyright information

© The Japanese Society for Clinical Molecular Morphology 2019

Authors and Affiliations

  • Takahiko Sakaue
    • 1
    • 2
  • Hironori Koga
    • 1
    • 2
    Email author
  • Hideki Iwamoto
    • 1
    • 2
  • Toru Nakamura
    • 1
    • 2
  • Yu Ikezono
    • 1
    • 2
  • Mitsuhiko Abe
    • 1
    • 2
  • Fumitaka Wada
    • 1
    • 2
  • Atsutaka Masuda
    • 1
    • 2
  • Toshimitsu Tanaka
    • 1
    • 2
    • 3
  • Masaru Fukahori
    • 1
    • 3
  • Tomoyuki Ushijima
    • 1
    • 3
  • Yuutarou Mihara
    • 4
  • Yoshiki Naitou
    • 4
    • 5
  • Yoshinobu Okabe
    • 1
  • Tatsuyuki Kakuma
    • 6
  • Keisuke Ohta
    • 7
  • Kei-ichiro Nakamura
    • 7
  • Takuji Torimura
    • 1
    • 2
  1. 1.Division of Gastroenterology, Department of MedicineKurume University School of MedicineKurumeJapan
  2. 2.Liver Cancer Research DivisionKurume University Research Center for Innovative Cancer TherapyKurumeJapan
  3. 3.Center for Multidisciplinary Treatment of CancerKurume University HospitalKurumeJapan
  4. 4.Department of PathologyKurume University School of MedicineKurumeJapan
  5. 5.Department of Diagnostic PathologyKurume University HospitalKurumeJapan
  6. 6.Biostatistics CenterKurume UniversityKurumeJapan
  7. 7.Division of Microscopic and Developmental Anatomy, Department of AnatomyKurume University School of MedicineKurumeJapan

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