Digestive Diseases and Sciences

, Volume 63, Issue 7, pp 1868–1877 | Cite as

Pyruvate Kinase Isozyme M2 Plays a Critical Role in the Interactions Between Pancreatic Stellate Cells and Cancer Cells

  • Atsushi Masamune
  • Shin Hamada
  • Naoki Yoshida
  • Tatsuhide Nabeshima
  • Tooru Shimosegawa
Original Article



The interaction between pancreatic cancer cells and pancreatic stellate cells plays a pivotal role in the progression of pancreatic cancer. Pyruvate kinase isozyme M2 is a key enzyme in glycolysis. Previous studies have shown that pyruvate kinase isozyme M2 is overexpressed in pancreatic cancer and that it regulates the aggressive behaviors of pancreatic cancer cells.


To clarify the role of pyruvate kinase isozyme M2 in the interactions between pancreatic cancer cells and pancreatic stellate cells.


Pyruvate kinase isozyme M2-knockdown pancreatic cancer cells (Panc-1 and SUIT-2 cells) and pancreatic stellate cells were generated by the introduction of small interfering RNA-expressing vector against pyruvate kinase isozyme M2. Cell proliferation, migration, and epithelial–mesenchymal transition were examined in vitro. The impact of pyruvate kinase isozyme M2 knockdown on the growth of subcutaneous tumors was examined in nude mice in vivo.


Pyruvate kinase isozyme M2-kockdown pancreatic cancer cells and pancreatic stellate cells showed decreased proliferation and migration compared to their respective control cells. Pancreatic stellate cell-induced proliferation, migration, and epithelial–mesenchymal transition were inhibited when pyruvate kinase isozyme M2 expression was knocked down in pancreatic cancer cells. In vivo, co-injection of pancreatic stellate cells increased the size of the tumor developed by the control SUIT-2 cells, but the effects were less evident when pyruvate kinase isozyme M2 was knocked down in SUIT-2 cells or pancreatic stellate cells.


Our results suggested a critical role of pyruvate kinase isozyme M2 in the interaction between pancreatic cancer cells and pancreatic stellate cells.


Desmoplastic reaction Fibrosis Myofibroblast Pancreatic ductal adenocarcinoma 





Conditioned medium


Epithelial–mesenchymal transition


Optical density


Pancreatic cancer cells


Pyruvate kinase isozyme M2


Pancreatic stellate cells


Standard error


Small interfering RNA


Signal transducer and activator of transcription



The authors are grateful to Shizuka Aoki for the excellent technical assistance.


This study was supported in part by JSPS (KAKENHI) (26293171, 26461029, 15H04804), the Mitsui Life Social Welfare Foundation (to A. Masamune), the Smoking Research Foundation (to A. Masamune), and the Pancreas Research Foundation of Japan (to N. Yoshida).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Atsushi Masamune
    • 1
  • Shin Hamada
    • 1
  • Naoki Yoshida
    • 1
  • Tatsuhide Nabeshima
    • 1
  • Tooru Shimosegawa
    • 1
  1. 1.Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan

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