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Induction of endothelial cell apoptosis by solid tumor cells
F Kebers1, J M Lewalle, J Desreux
1Laboratory of Biology, University of Liège, Belgium.
Experimental Cell Research
|May 23, 1998
Summary
Solid tumor cells, but not blood cells, induce endothelial cell apoptosis through direct contact, potentially explaining tumor cell extravasation and metastasis. This research clarifies mechanisms of metastasis.
Area of Science:
- Oncology
- Cell Biology
- Vascular Biology
Background:
- Tumor cell extravasation mechanisms driving metastasis are not fully understood.
- Endothelial cell integrity is known to be compromised by tumor cell interactions with the vascular wall.
Purpose of the Study:
- To investigate the impact of breast adenocarcinoma MCF-7 cells on the apoptosis of human umbilical vein endothelial cells (HUVEC).
- To differentiate the endothelial cell-damaging effects of solid tumor cells from those of normal or hematopoietic cells.
Main Methods:
- TUNEL labeling, nuclear morphology assessment, and DNA electrophoresis were used to quantify HUVEC apoptosis.
- Caspase-3 activity was measured.
- Co-culture experiments and conditioned media assays were performed to assess the role of cell-to-cell contact.
Main Results:
- MCF-7 cells significantly increased HUVEC apoptosis (two- to fourfold) and caspase-3 activity.
- Normal cells and malignant hematopoietic cells did not induce HUVEC apoptosis.
- Other solid tumor-derived cells (MDA-MB-231, T47D, HT 1080) mimicked MCF-7 cells' apoptotic effect on HUVEC.
- Apoptosis induction required direct cell-to-cell contact.
Conclusions:
- Solid tumor cells can induce endothelial cell apoptosis, potentially compromising vascular integrity during extravasation.
- Leukocytes may use different mechanisms for extravasation that do not involve endothelial cell damage.
- Findings provide insights into the molecular mechanisms underlying tumor cell extravasation and metastasis.