Altered glucose metabolism and proteolysis in pancreatic cancer cell conditioned myoblasts: searching for a gene expression pattern with a microarray analysis of 5000 skeletal muscle genes.
OBJECTIVE
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.
Basso
D
D
Department of Laboratory Medicine, University of Padova, Italy.
Millino
C
C
Greco
E
E
Romualdi
C
C
Fogar
P
P
Valerio
A
A
Bellin
M
M
Zambon
C-F
CF
Navaglia
F
F
Dussini
N
N
Avogaro
A
A
Pedrazzoli
S
S
Lanfranchi
G
G
Plebani
M
M
D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D052138:Genes, Neoplasm / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D019344:Lactic Acid / Q000032:analysis; D008297:Male; D051379:Mice; D008875:Middle Aged; D032446:Myoblasts / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D017077:Culture Media, Conditioned; D019344:Lactic Acid; D005947:Glucose