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There is considerable evidence to suggest that epidermal growth factor (EGF) and its receptor (EGFr) play an important role in tissue repair, cell proliferation and migration. EGF also inhibits acid production and imparts a cytoprotective mechanism against refluxed gastric contents entering the oesophagus.
Alginate biopolymers are widely used in the treatment of Gastrooesophageal Reflux Disease (GORD). Like EGF they have cytoprotective biological effects although their mechanism(s) of action have not been specifically identified. Alginate biopolymers up-regulate endocytosis, although this activity is not strictly dependent on the interaction of EGF with its receptor. There is, however, evidence of a co-operative relationship.
The action of EGF is due to the ligand binding to its receptor, EGFr, resulting in its activation, generating membrane signalling and subsequent internalisation of EGF and the receptor. Glycolipids are involved in the transport of proteins in the endocytic pathway. We have evidence to suggest that glycolipids such as gangliosides GM1 and GM3 may participate in the regulation of EGF/EGFr mediated endocytosis. It is known that GM3inhibits EGF.
In our study we have examined four cell lines derived from oesophageal carcinomas (2 squamous cell carcinomas and 2 adenocarcinomas). Direct immunofluorescence protocols with confocal microscopy and FACScan® techniques have been employed to observe the relationship between EGF, alginate, EGFr and gangliosides.
Results: Alginate up-regulates fluid phase endocytosis. EGF up-regulates fluid phase endocytosis. EGF and alginate up regulates fluid phase endocytosis. Alginate does not up-regulate receptor mediated endocytosis.
256. CO-CULTURE OF HUMAN SQUAMOUS OESOPHAGEAL AND FIBROBLAST CELL LINES IN ACTIVATION OF PROMMP-2 RESULTING IN A DOWN REGULATION OF INTEGRIN αVβ3 EXPRESSION AND MMP-2, MT1-MMP EXPRESSION
Background and aims: Over expression of various matrix metalloproteinases (MMPs) and decreased expression of tissue inhibitors of metalloproteinases (TIMPs) have previously been speculated to correlate with tumour progression in a variety of cancers. The aim of this study was to investigate MT1-MMP and αVβ3 interactions in the activation of MMPs in human oesophageal cancer cell lines during co-culture with …