Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness

Mark S. Duxbury; Talat Waseem; Hiromichi Ito; Malcolm K. Robinson; Michael J. Zinner; Stanley W. Ashley; Edward E. Whang

doi:10.1016/j.bbrc.2003.08.024

Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness

Mark S. Duxbury, Talat Waseem, Hiromichi Ito, Malcolm K. Robinson, Michael J. Zinner, Stanley W. Ashley, Edward E. Whang

School of Medicine

Research output: Contribution to journal › Article › peer-review

138 Scopus citations

Abstract

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 (0-100nM). 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.

Original language	English (US)
Pages (from-to)	464-468
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	309
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2003.08.024
State	Published - Sep 19 2003

Keywords

Akt
BxPc3
Cachexia
Cancer
Capan2
GHS-R
Ghrelin
Invasion
MIAPaCa2
PANC1
Pancreatic adenocarcinoma

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2003.08.024

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title = "Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness",

abstract = "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 (0-100nM). 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.",

keywords = "Akt, BxPc3, Cachexia, Cancer, Capan2, GHS-R, Ghrelin, Invasion, MIAPaCa2, PANC1, Pancreatic adenocarcinoma",

author = "Duxbury, {Mark S.} and Talat Waseem and Hiromichi Ito and Robinson, {Malcolm K.} and Zinner, {Michael J.} and Ashley, {Stanley W.} and Whang, {Edward E.}",

note = "Funding Information: This study was supported by a grant from the National Pancreas Foundation and by National Institute of Health Grants DK02786 (E.E.W.) and DK47326 (S.W.A.). The authors gratefully acknowledge the technical support of Jan Rounds.",

year = "2003",

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doi = "10.1016/j.bbrc.2003.08.024",

language = "English (US)",

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T1 - Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness

AU - Duxbury, Mark S.

AU - Waseem, Talat

AU - Ito, Hiromichi

AU - Robinson, Malcolm K.

AU - Zinner, Michael J.

AU - Ashley, Stanley W.

AU - Whang, Edward E.

N1 - Funding Information: This study was supported by a grant from the National Pancreas Foundation and by National Institute of Health Grants DK02786 (E.E.W.) and DK47326 (S.W.A.). The authors gratefully acknowledge the technical support of Jan Rounds.

PY - 2003/9/19

Y1 - 2003/9/19

N2 - 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 (0-100nM). 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.

AB - 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 (0-100nM). 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.

KW - Akt

KW - BxPc3

KW - Cachexia

KW - Cancer

KW - Capan2

KW - GHS-R

KW - Ghrelin

KW - Invasion

KW - MIAPaCa2

KW - PANC1

KW - Pancreatic adenocarcinoma

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SN - 0006-291X

VL - 309

SP - 464

EP - 468

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness

Abstract

Keywords

ASJC Scopus subject areas

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