A comparative study of the mitogenic and morphogenic effects of epidermal growth factor and amphiregulin on colonic carcinoma cells
A comparative study of the mitogenic and morphogenic effects of epidermal growth factor and amphiregulin on colonic carcinoma cells
Two morphologically distinct cell lines showing no gross genetic differences were cloned from a single adenocarcinoma of the colon and used to study the effects of members of the EGFR ligand family. These cell lines, named GP2d and GP5d, were characterised with respect to their EGFR complement and ligand expression, and were shown to differ in their expression of amphiregulin (AR).
The morphological effects induced by EGF resembled the epithelial-mesenchymal transition of the embryo and were characterised by a marked reduction in cell-cell contact and enhanced spreading. These changes were accompanied by regulation of the expression and redistribution of several adhesion molecules involved in cell adhesion. E-cadherin was redistributed and α2-integrain upregulated. EGF treatment resulted in phenotypic changes that are important for tumour dissemination.
Two other EGFR ligands tested, TGFα and HB-EGF, also elicited similar morphogenic and proliferative effects to EGF. However, AR behaved in marked contrast. It was able to stimulate ADG and AIG of both cell lines over a wide concentration range. However, it was a poor morphogenic agent, unless proliferation was inhibited by pharmacological intervention. Thus AR alone was shown to have little effect on e-cadherin distribution and α2-integrin expression until used at supraphysioligcal conditions. The differences between the responses of EGF and AR explored by using a mutant ligand for the receptor, EGFL47A. In common with AR, this ligand has reduced affinity for the receptor, however it is distinct from AR by its lack of the N-terminal heparin-binding domain. Like AR, EGFL47A weakly stimulated ADG and did not inhibit AIG. In contrast to AR, it partially reproduced the morphogenic response of EGF on the GP cells.
The differential abilities of EGF and AR to elicit changes in cellular morphology, adhesion molecule expression and distribution, and cell migration suggest that these ligands may play distinct roles in tumour cell proliferation and dissemination.
University of Southampton
Solic, Nicola
e8808086-3cda-43c1-a122-681908c9a4f3
1999
Solic, Nicola
e8808086-3cda-43c1-a122-681908c9a4f3
Solic, Nicola
(1999)
A comparative study of the mitogenic and morphogenic effects of epidermal growth factor and amphiregulin on colonic carcinoma cells.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Two morphologically distinct cell lines showing no gross genetic differences were cloned from a single adenocarcinoma of the colon and used to study the effects of members of the EGFR ligand family. These cell lines, named GP2d and GP5d, were characterised with respect to their EGFR complement and ligand expression, and were shown to differ in their expression of amphiregulin (AR).
The morphological effects induced by EGF resembled the epithelial-mesenchymal transition of the embryo and were characterised by a marked reduction in cell-cell contact and enhanced spreading. These changes were accompanied by regulation of the expression and redistribution of several adhesion molecules involved in cell adhesion. E-cadherin was redistributed and α2-integrain upregulated. EGF treatment resulted in phenotypic changes that are important for tumour dissemination.
Two other EGFR ligands tested, TGFα and HB-EGF, also elicited similar morphogenic and proliferative effects to EGF. However, AR behaved in marked contrast. It was able to stimulate ADG and AIG of both cell lines over a wide concentration range. However, it was a poor morphogenic agent, unless proliferation was inhibited by pharmacological intervention. Thus AR alone was shown to have little effect on e-cadherin distribution and α2-integrin expression until used at supraphysioligcal conditions. The differences between the responses of EGF and AR explored by using a mutant ligand for the receptor, EGFL47A. In common with AR, this ligand has reduced affinity for the receptor, however it is distinct from AR by its lack of the N-terminal heparin-binding domain. Like AR, EGFL47A weakly stimulated ADG and did not inhibit AIG. In contrast to AR, it partially reproduced the morphogenic response of EGF on the GP cells.
The differential abilities of EGF and AR to elicit changes in cellular morphology, adhesion molecule expression and distribution, and cell migration suggest that these ligands may play distinct roles in tumour cell proliferation and dissemination.
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Published date: 1999
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Local EPrints ID: 463972
URI: http://eprints.soton.ac.uk/id/eprint/463972
PURE UUID: 7bea4b82-d0c7-4b46-9243-d05e943cca6d
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Date deposited: 04 Jul 2022 20:59
Last modified: 04 Jul 2022 20:59
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Author:
Nicola Solic
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