title: Diabetogenic glucose and insulin concentrations modulate transcriptome and protein levels involved in tumour cell migration, adhesion and proliferation.
abstract: BACKGROUND
  During the last decade, epidemiological studies uncovered the tremendous impact of metabolic syndrome/diabetes mellitus type 2 (DM T2) as risk factors of the progression of cancer. Therefore, we studied the impact of diabetogenic glucose and insulin concentrations on the activities of tumour cells, because little is known about how high glucose and insulin levels are influencing gene activities causing changes in the signal cascade activities with respect to kinases involved in the proliferation and migration of cancer cells.
  
  
  METHODS
  To address this question we analysed the activity of more than 400 gene signatures related to (i) cell cycle, (ii) cell movement as well as (iii) signal transduction. We examined transcriptomes of kinases (PKCα, PI3K), cadherins (E-, N- VE-), integrins and cyclins by comparing physiological (5.5 mM) vs diabetogenic (11 mM) glucose concentrations (without and with insulin).
  
  
  RESULTS
  Proliferation assays revealed that high levels of glucose (11 mM) and insulin (100 ng ml(-1)) did promote the proliferation of the tumour cell lines HT29, SW480, MCF-7, MDA MB468, PC3 and T24. Using a 3D-migration assay, we have shown that high glucose concentrations caused increased motility rates of the tumour cells. The increase in migratory activity at high glucose and insulin concentrations was mediated by an activation of PI3K, PKCα and MLCK, as figured out by the pharmacological inhibitors wortmannin, Go6976 and ML-7.
  
  
  CONCLUSIONS
  We present molecular and functional data, which could help to understand how hyperglycaemia and hyperinsulinemia might trigger tumour cell proliferation and motility in patients, too.
authors.affiliation: Institute of Immunology and Experimental Oncology, University Witten/Herdecke, Stockumer Str. 10, Witten 58448, Germany. kai.masur@inp-greifswald.de
authors.forename: K
authors.initials: K
authors.lastname: Masur
authors.forename: C
authors.initials: C
authors.lastname: Vetter
authors.forename: A
authors.initials: A
authors.lastname: Hinz
authors.forename: N
authors.initials: N
authors.lastname: Tomas
authors.forename: H
authors.initials: H
authors.lastname: Henrich
authors.forename: B
authors.initials: B
authors.lastname: Niggemann
authors.forename: K S
authors.initials: KS
authors.lastname: Zänker
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003920:Diabetes Mellitus / Q000378:metabolism*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007328:Insulin / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin