| Summary: | 碩士 === 國立成功大學 === 生理學研究所 === 84 === In this study, I attempted to investigate the response of
epithelial cellswhen they interact with the extracellular matrix
in an inappropriate orient-ation. Cell lines of epithelial
(MDCK, LLC-PK1), endothelial (BAEC) and mesen-chymal (ESK-4 and
NIH-3T3) origins were employed. Under collagen gel overlay,MDCK
cells lost the epithelial morphology and underwent cell-cell
dissociationas early as 12 hr and they transformed into tubule-
like structure at about 24hr. However,they developed apoptosis,
as confirmed by fragmented DNA analysis,Hoechst 33258 staning
and also flow cytometrical analysis, within 24-48 hrafter
collagen gel overlay. Finally, widespread of apoptosis was
observedwithin 3 days of collagen overlay. The cell death was
not caused by the physi-cal effect (eg. gravity), because
agarose gel overlay did not induce any mor-phological changes.
LLC-PK1 and BAEC cells also developed similar phenomenon.In
contrast, collagen gel overlay did not inhibit the growth of
fibroblasts atall. The collagen gel overlay-induced apoptosis
seems to be a unique phenome-non for polarized cells. We have
termed this phenomenon as "disoriented celldeath".
Furthermoore, cycloheximide-treated MDCK cells could circumvent
dis-oriented cell death, indicating that newly synthesized
proteins were involvedin the mechanism. Neither the treatment
of scatter factor (HGF), nor low celldensity could prevent MDCK
cells from disoriented cell death. However, over-expression of
bcl-2 conferred resistance to disoriented cell death. Finally,
since disoriented cell death could be alleviated by
monoclonal antibodiesagainst a2 integrin subunit, signals
tranduced from a2 integrin seemed to me-diate collagen gel
overlay-induced response.
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