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Micro-encapsulation of MDCK-ras-e cells prevents loss of E-cadherin invasion-suppressor function in vivo
G M Vandenbossche1, G K De Bruyne, E A Bruyneel
1Laboratory of Pharmaceutical Technology, University of Ghent, Belgium.
Abstract:
The invasion-suppressor molecule E-cadherin mediates Ca(2+)-dependent cell aggregation and prevents invasion. E-cadherin-positive Madin-Darby canine kidney (MDCK) cells that were non-invasive in vitro formed, upon i.p. injection, tumors that were invasive. Differentiated tubular tumor areas showed an intense immuno-signal for E-cadherin at intercellular contacts, whereas undifferentiated structures did not. Cell lines derived from such tumors turned out to be invasive in vitro and showed decreased Ca(2+)-dependent cell aggregation but no change in E-cadherin immunopositivity. This combination of phenotypes indicated a loss of the E-cadherin invasion-suppressor function. Micro-encapsulation of i.p.-injected cells prevented the loss of the E-cadherin invasion-suppressor function. We concluded that this loss in vivo was dependent upon immediate contacts between tumor cells and host cells or upon host factors that could not cross the capsule membrane.
Insights
E-cadherin normally prevents cell invasion, but in vivo, its suppressor function is lost. Micro-encapsulation preserved E-cadherin function, suggesting host cell contact or factors are responsible for invasion.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- E-cadherin is a key invasion-suppressor molecule mediating calcium-dependent cell aggregation.
- Non-invasive E-cadherin-positive Madin-Darby canine kidney (MDCK) cells can form invasive tumors in vivo.
Purpose of the Study:
- To investigate the loss of E-cadherin's invasion-suppressor function in vivo.
- To identify factors contributing to the loss of E-cadherin function during tumor formation.
Main Methods:
- In vitro assessment of cell aggregation and invasion.
- In vivo tumor formation via intraperitoneal (i.p.) injection of MDCK cells.
- Immunohistochemical analysis of E-cadherin expression in tumor tissues.
- Micro-encapsulation techniques to isolate injected cells from host environment.
Main Results:
- MDCK cells formed invasive tumors in vivo despite initial E-cadherin positivity.
- Loss of E-cadherin invasion-suppressor function correlated with undifferentiated tumor structures.
- Derived cell lines showed reduced cell aggregation but maintained E-cadherin immunopositivity.
- Micro-encapsulation prevented the loss of E-cadherin function, indicating a role for host interactions.
Conclusions:
- In vivo tumor formation leads to a loss of E-cadherin's invasion-suppressor function.
- This loss is dependent on direct contact with host cells or diffusible host factors.
- Micro-encapsulation preserves E-cadherin function by preventing critical in vivo interactions.