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

Abstract

Background

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.

Aims

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

Methods

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.

Results

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.

Conclusions

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

Keywords

Desmoplastic reaction Fibrosis Myofibroblast Pancreatic ductal adenocarcinoma 

Abbreviations

BrdU

5-Bromo-2′-deoxyuridine

CM

Conditioned medium

EMT

Epithelial–mesenchymal transition

OD

Optical density

PCCs

Pancreatic cancer cells

PKM2

Pyruvate kinase isozyme M2

PSCs

Pancreatic stellate cells

SE

Standard error

siRNA

Small interfering RNA

STAT3

Signal transducer and activator of transcription

Notes

Acknowledgments

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

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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