Cross-talk between human airway epithelial cells and 3T3-J2 feeder cells involves partial activation of human MET by murine HGF.

PloS One
Robert E HyndsSam M Janes

Abstract

There is considerable interest in the ex vivo propagation of primary human basal epithelial stem/progenitor cells with a view to their use in drug development, toxicity testing and regenerative medicine. These cells can be expanded in co-culture with mitotically inactivated 3T3-J2 murine embryonic feeder cells but, similar to other epithelial cell culture systems employing 3T3-J2 cells, the aspects of cross-talk between 3T3-J2 cells and human airway basal cells that are critical for their expansion remain largely unknown. In this study, we investigated secreted growth factors that are produced by 3T3-J2 cells and act upon primary human airway basal cells. We found robust production of hepatocyte growth factor (HGF) from fibroblast feeder cells following mitotic inactivation. Consistent with the limited cross-species reactivity of murine HGF on the human HGF receptor (MET; HGFR), MET inhibition did not affect proliferative responses in human airway basal cells and HGF could not replace feeder cells in this culture system. However, we found that murine HGF is not completely inactive on human airway epithelial cells or cancer cell lines but stimulates the phosphorylation of GRB2-associated-binding protein 2 (GAB2) and signal trans...Continue Reading

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Citations

Jun 9, 2020·Clinical and Translational Medicine·Wei LiuXinghuan Wang
Mar 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ersilia NigroSeverina Pacifico

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Datasets Mentioned

BETA
GTX113273

Methods Mentioned

BETA
biopsies
profiler
X-ray
Transfection
ubiquitination
ELISA
nuclear translocation
co-immunoprecipitation
immunoprecipitation

Software Mentioned

GraphPad Prism
TreeStar
FlowJo

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