title: In vivo factors influencing tumour M2-pyruvate kinase level in human pancreatic cancer cell lines.
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.
authors.affiliation: University Department of Surgery, Royal Free and University College Medical School of UCL, 9th Floor, Pond Street, London, NW3 2QG, UK.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Kumar
authors.forename: Sybille
authors.initials: S
authors.lastname: Mazurek
authors.forename: Shiyu
authors.initials: S
authors.lastname: Yang
authors.forename: Klaus
authors.initials: K
authors.lastname: Failing
authors.forename: Marc
authors.initials: M
authors.lastname: Winslet
authors.forename: Barry
authors.initials: B
authors.lastname: Fuller
authors.forename: Brian R
authors.initials: BR
authors.lastname: Davidson
mesh_terms: D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010190:Pancreatic Neoplasms / Q000201:enzymology*; D055503:Protein Multimerization; D011770:Pyruvate Kinase / Q000032:analysis* / Q000737:chemistry
chemical_list: D011770:Pyruvate Kinase; D005947:Glucose