Glucagon-like petide-2 acts on colon cancer myofibroblasts to stimulate proliferation, migration and invasion of both myofibroblasts and cancer cells via the IGF pathway

Marianne Shawe-Taylor, J. Dinesh Kumar, Whitney Holden, Steven Dodd, Akos Varga, Olivier Giger, A. Varró, Graham J. Dockray

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Glucagon-like peptide (GLP)-2 stimulates intestinal epithelial proliferation by acting, in part, via IGF release from sub-epithelial myofibroblasts. The response of myofibroblasts to GLP-2 remains incompletely understood. We studied the action of GLP-2 on myofibroblasts from colon cancer and adjacent tissue, and the effects of conditioned medium from these cells on epithelial cell proliferation, migration and invasion. GLP-2 stimulated proliferation, migration and invasion of myofibroblasts and the proliferative and invasive responses of cancer-associated myofibroblasts were greater than those of myofibroblasts from adjacent tissue. The responses were inhibited by an IGF receptor inhibitor, AG1024. Conditioned medium from GLP-2 treated myofibroblasts increased proliferation, migration and invasion of SW480, HT29, LoVo epithelial cells and these responses were inhibited by AG1024; GLP-2 alone had no effect on these cells. In addition, when myofibroblasts and epithelial cells were co-cultured in Ibidi chambers there was mutual stimulation of migration in response to GLP-2. The latter increased both IGF-1 and IGF-2 transcript abundance in myofibroblasts. Moreover, a number of IGF binding proteins (IGFBP-4, −5, −7) were identified in myofibroblast medium; in the presence of GLP-2 there was increased abundance of the cleavage products of IGBBP-4 and IGFBP-5 suggesting activation of a degradation mechanism that might increase IGF bioavailability. The data suggest that GLP-2 stimulates cancer myofibroblast proliferation, migration and invasion; GLP-2 acts indirectly on epithelial cells partly via increased IGF expression in myofibroblasts and partly, perhaps, by increased bioavailability through degradation of IGFBPs.

Original languageEnglish
Pages (from-to)49-57
Number of pages9
JournalPeptides
Volume91
DOIs
Publication statusPublished - May 1 2017

Fingerprint

Glucagon-Like Peptide 2
Myofibroblasts
Glucagon
Colonic Neoplasms
Cells
Neoplasms
Epithelial Cells
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor Binding Protein 4
Conditioned Culture Medium
Biological Availability
Tissue
Degradation
Insulin-Like Growth Factor II
Cell proliferation
Insulin-Like Growth Factor I

Keywords

  • GLP-2
  • IGF
  • IGFBP
  • Myofibroblast migration
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

Cite this

Glucagon-like petide-2 acts on colon cancer myofibroblasts to stimulate proliferation, migration and invasion of both myofibroblasts and cancer cells via the IGF pathway. / Shawe-Taylor, Marianne; Kumar, J. Dinesh; Holden, Whitney; Dodd, Steven; Varga, Akos; Giger, Olivier; Varró, A.; Dockray, Graham J.

In: Peptides, Vol. 91, 01.05.2017, p. 49-57.

Research output: Contribution to journalArticle

Shawe-Taylor, Marianne ; Kumar, J. Dinesh ; Holden, Whitney ; Dodd, Steven ; Varga, Akos ; Giger, Olivier ; Varró, A. ; Dockray, Graham J. / Glucagon-like petide-2 acts on colon cancer myofibroblasts to stimulate proliferation, migration and invasion of both myofibroblasts and cancer cells via the IGF pathway. In: Peptides. 2017 ; Vol. 91. pp. 49-57.
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AB - Glucagon-like peptide (GLP)-2 stimulates intestinal epithelial proliferation by acting, in part, via IGF release from sub-epithelial myofibroblasts. The response of myofibroblasts to GLP-2 remains incompletely understood. We studied the action of GLP-2 on myofibroblasts from colon cancer and adjacent tissue, and the effects of conditioned medium from these cells on epithelial cell proliferation, migration and invasion. GLP-2 stimulated proliferation, migration and invasion of myofibroblasts and the proliferative and invasive responses of cancer-associated myofibroblasts were greater than those of myofibroblasts from adjacent tissue. The responses were inhibited by an IGF receptor inhibitor, AG1024. Conditioned medium from GLP-2 treated myofibroblasts increased proliferation, migration and invasion of SW480, HT29, LoVo epithelial cells and these responses were inhibited by AG1024; GLP-2 alone had no effect on these cells. In addition, when myofibroblasts and epithelial cells were co-cultured in Ibidi chambers there was mutual stimulation of migration in response to GLP-2. The latter increased both IGF-1 and IGF-2 transcript abundance in myofibroblasts. Moreover, a number of IGF binding proteins (IGFBP-4, −5, −7) were identified in myofibroblast medium; in the presence of GLP-2 there was increased abundance of the cleavage products of IGBBP-4 and IGFBP-5 suggesting activation of a degradation mechanism that might increase IGF bioavailability. The data suggest that GLP-2 stimulates cancer myofibroblast proliferation, migration and invasion; GLP-2 acts indirectly on epithelial cells partly via increased IGF expression in myofibroblasts and partly, perhaps, by increased bioavailability through degradation of IGFBPs.

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