Tumor Biology

, Volume 31, Issue 2, pp 69–77 | Cite as

In vivo factors influencing tumour M2-pyruvate kinase level in human pancreatic cancer cell lines

  • Yogesh Kumar
  • Sybille Mazurek
  • Shiyu Yang
  • Klaus Failing
  • Marc Winslet
  • Barry Fuller
  • Brian R. Davidson
Research Article

Abstract

In tumour cells, the tetramer/dimer ratio of the pyruvate kinase isoenzyme type M2 (M2-PK) determines whether glucose carbons are degraded to lactate with production of energy (tetrameric form) or are channelled into synthetic processes (dimeric form). The influence of different tumour microenvironment conditions on the tetramer/dimer ratio of M2-PK and cell doublings were investigated in a non-metastatic and metastatic pancreatic cancer cell line. The metastatic Colo357 cells contained about fourfold more M2-PK protein and about 3.5-fold more dimeric M2-PK than the non-metastatic Panc-1 cells. In Colo357 cells hypoxia, glucose starvation as well as acidification induced an increase of the dimeric form of M2-PK, whereas in Panc-1 cells no effect on M2-PK was observed. Under hypoxia in Colo357 cells, the dimerization and inactivation of M2-PK results in an inhibition of cell proliferation, whereas under glucose starvation and acidification the dimerization of M2-PK allowed further cell doublings. M2-PK expression and the quaternary structure of M2-PK are influenced by the tumour metastatic potential. The quaternary structure of M2-PK may be differently affected by hypoxia, glucose starvation and acidification with severe consequences on cell doublings.

Keywords

pyruvate kinase M2 Tumour M2-PK Tumour microenvironment Pancreatic cancer 

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • Yogesh Kumar
    • 1
  • Sybille Mazurek
    • 2
    • 3
  • Shiyu Yang
    • 1
  • Klaus Failing
    • 4
  • Marc Winslet
    • 1
  • Barry Fuller
    • 1
  • Brian R. Davidson
    • 1
  1. 1.University Department of SurgeryRoyal Free and University College Medical School of UCLLondonUK
  2. 2.Institute of Biochemistry and Endocrinology, Veterinary FacultyUniversity of GiessenGiessenGermany
  3. 3.ScheBo Biotech AGGiessenGermany
  4. 4.Unit of Biomathematics, Veterinary FacultyUniversity of GiessenGiessenGermany

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