Receptors and ligands for autocrine growth pathways are up-regulated when pancreatic cancer cells are adapted to serum-free culture.
Overexpression of autocrine growth factors and their receptors has been reported in many human cancers. The study of autocrine-regulated pathways using in vitro culture systems can be hindered by the presence of fetal bovine serum in culture medium. A human pancreatic cancer cell line (HPAF) was slowly weaned from its dependence on fetal bovine serum and subsequently maintained in serum-free conditions. Growth factor secretion studies showed that production of autocrine growth factors such as transforming growth factor alpha, gastrin-releasing peptide, and insulin-like growth factor I from weaned cells increased three times compared with nonweaned cells (p < 0.01). The epidermal growth factor and gastrin-releasing peptide receptor densities were also increased in weaned cells (2 times and 2.5 times, respectively, p < 0.05). The proliferation of weaned cells cultured continuously in the same medium was significantly greater than of nonweaned cells (p < 0.05). Collectively, these data indicate that weaned pancreatic cancer cells can proliferate in the absence of serum by up-regulating autocrine pathways.
Murphy
L O
LO
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
Abdel-Wahab
Y H
YH
Wang
Q J
QJ
Knezetic
J A
JA
Permnert
J
J
Larsson
J
J
Hollingsworth
A M
AM
Adrian
T E
TE
D001667:Binding, Competitive; D001839:Bombesin / Q000096:biosynthesis; D002455:Cell Division; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D004815:Epidermal Growth Factor / Q000096:biosynthesis; D066246:ErbB Receptors / Q000235:genetics; D019886:Gastrin-Releasing Peptide / Q000096:biosynthesis; D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D018004:Receptors, Bombesin / Q000096:biosynthesis / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D006133:Growth Substances; D012333:RNA, Messenger; D018004:Receptors, Bombesin; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D019886:Gastrin-Releasing Peptide; D066246:ErbB Receptors; D001839:Bombesin