Article Text
Abstract
Background and aims: We verified whether conditioned media (CM) from pancreatic cancer cell lines (MIAPaCa2, CAPAN-1, PANC-1, BxPC3) alter glucose metabolism and gene expression profiles (microarray experiment with a platform of 5000 skeletal muscle cDNA) in mice myoblasts.
Methods: Myoblasts were incubated with control or pancreatic cancer CM for 24 and 48 hours.
Results: Lactate significantly increased in CM compared with non-conditioned myoblasts. No variations in expression levels of the main genes involved in glycolysis were found in CM myoblasts. Propionyl coenzyme A carboxylase and isocitrate dehydrogenase 3 beta genes, which encode enzymes of the tricarboxylic acid cycle, were overexpressed, while IGFIIR and VAMP5 genes were underexpressed in CM myoblasts. PAFAH1B1 and BCL-2 genes (intracellular signal transduction) and the serine protease cathepsin G (proteolysis), were overexpressed in CM myoblasts. Tyrosine accumulation in CM myoblasts suggested that proteolysis overcomes protein synthesis. Sorcin, actin alpha, troponin T1, and filamin A were underexpressed in CM myoblasts.
Conclusions: Our findings demonstrate that pancreatic cancer cell conditioned media enhanced lactate production and induced proteolysis, possibly by altering expression levels of a large number of genes, not only those involved in protein biosynthesis and degradation or glucose metabolism, but also those involved in the tricarboxylic acid cycle and in vesicle traffic.
- CM, conditioned media
- DMEM, Dulbecco’s modified Eagle’s medium
- FCS, fetal calf serum
- PBS, phosphate buffered saline
- NCM, non-conditioned medium
- TC, tumour conditioned
- MW, molecular weight
- RT-PCR, reverse transcription-polymerase chain reaction
- ECHS1, enoyl coenzyme A hydratase
- IGF2R, insulin-like growth factor 2 receptor
- VAMP5, vesicle associated membrane protein 5
- FLNA, filamin A
- PCCB, propionyl coenzyme A carboxylase
- RPS16, ribosomal protein S16
- cachexia
- diabetes mellitus
- micoarray
- myoblasts
- pancreatic cancer
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- CM, conditioned media
- DMEM, Dulbecco’s modified Eagle’s medium
- FCS, fetal calf serum
- PBS, phosphate buffered saline
- NCM, non-conditioned medium
- TC, tumour conditioned
- MW, molecular weight
- RT-PCR, reverse transcription-polymerase chain reaction
- ECHS1, enoyl coenzyme A hydratase
- IGF2R, insulin-like growth factor 2 receptor
- VAMP5, vesicle associated membrane protein 5
- FLNA, filamin A
- PCCB, propionyl coenzyme A carboxylase
- RPS16, ribosomal protein S16