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Induction of contact‐dependent endothelial apoptosis by osteosarcoma cells suggests a role for endothelial cell apoptosis in blood‐borne metastasis
Author(s) -
McEwen A,
Emmanuel C,
Medbury H,
Leick A,
Walker DM,
Zoellner H
Publication year - 2003
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1457
Subject(s) - apoptosis , angiogenesis , biology , endothelial stem cell , umbilical vein , cell culture , flow cytometry , endothelium , cancer cell , microbiology and biotechnology , osteosarcoma , cell growth , metastasis , cancer research , pathology , immunology , cancer , medicine , in vitro , endocrinology , biochemistry , genetics
Although tumour cells are believed to migrate between endothelial cells early in metastasis, the possibility remains that endothelial apoptosis may also contribute to the tumour's breach of the vascular barrier. Although seemingly inconsistent with tumour angiogenesis, one publication describes the induction of contact‐dependent apoptosis in cultured endothelium by tumour cells. The cell culture data are, however, open to challenge on technical grounds while there are no confirmatory reports. The present paper describes experiments overcoming these limitations. SAOS‐2 human osteosarcoma cells and two rat carcinoma cell lines were co‐cultured with human umbilical vein endothelial cells (HUVECs) and cultures labelled by surface lectin histochemistry for endothelium. The HUVEC culture density was determined and SAOS‐2 cells, but not rat carcinoma cells, were found significantly to reduce HUVEC survival despite the release of potent growth factors as determined in separate experiments with tumour cell conditioned medium. Lectin labelling combined with light microscopy, transmission electron microscopy, flow cytometry for both lectin binding and DNA content, and DNA gel electrophoresis of SAOS‐2/HUVEC co‐cultures revealed extensive HUVEC apoptosis. These findings indicate contact‐dependent endothelial apoptosis by SAOS‐2, while this activity appeared weaker and overwhelmed by HUVEC proliferation with rat carcinoma cells. Importantly, this study supports the suggestion that endothelial apoptosis may be important for metastasis and suggests a complex interplay between endothelial proliferation and apoptosis in tumours. Copyright © 2003 John Wiley & Sons, Ltd.