Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness.
Ghrelin, a newly described potent orexigenic peptide, may have therapeutic potential in patients with cachexia. We assessed whether pancreatic adenocarcinoma, commonly associated with marked cachexia, is a ghrelin-responsive malignancy. Pancreatic adenocarcinoma cells were exposed to ghrelin (0-100 nM). Proliferation was determined by MTT assay. Ghrelin, ghrelin 1a and 1b receptor expression and Akt phosphorylation were assessed. The effects of ghrelin (+/- its antagonist D-Lys-GHRP6, or the PI3-K inhibitor Wortmannin) on cellular motility and invasiveness were quantified by Matrigel Boyden chamber assay. All cell lines expressed ghrelin 1a and 1b receptor transcript and protein, but only PANC1 weakly expressed ghrelin transcript. Ten nanomolar ghrelin increased proliferation, motility, invasiveness, and Akt phosphorylation in all cell lines. Proliferation was affected dose-dependently, being suppressed at higher ghrelin concentrations. D-Lys-GHRP6 suppressed ghrelin-induced proliferation, invasion, and Akt phosphorylation. Wortmannin abolished the effects of ghrelin on motility and invasiveness. Pancreatic adenocarcinoma is a ghrelin-responsive malignancy.
Duxbury
Mark S
MS
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Waseem
Talat
T
Ito
Hiromichi
H
Robinson
Malcolm K
MK
Zinner
Michael J
MJ
Ashley
Stanley W
SW
Whang
Edward E
EE
D000230:Adenocarcinoma / Q000150:complications / Q000473:pathology*; D000730:Androstadienes / Q000494:pharmacology; D002100:Cachexia / Q000188:drug therapy / Q000209:etiology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D054439:Ghrelin; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000150:complications / Q000473:pathology*; D036361:Peptide Hormones / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000077191:Wortmannin
D000730:Androstadienes; D054439:Ghrelin; D036361:Peptide Hormones; D000077191:Wortmannin