Induction of contact-dependent endothelial apoptosis by osteosarcoma cells suggests a role for endothelial cell apoptosis in blood-borne metastasis.
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.
The Cellular and Molecular Pathology Research Unit, The Department of Oral Medicine and Oral Pathology, Faculty of Dentistry, The University of Sydney, Westmead Centre for Oral Health, Westmead Hospital, Westmead, NSW 2145, Australia.
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McEwen
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Emmanuel
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Medbury
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Leick
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Walker
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Zoellner
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001859:Bone Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D002452:Cell Count; D018920:Coculture Techniques; D003470:Culture Media; D004273:DNA, Neoplasm / Q000032:analysis; D004587:Electrophoresis, Agar Gel / Q000379:methods; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology; D005434:Flow Cytometry / Q000379:methods; D037102:Lectins / Q000032:analysis; D008854:Microscopy, Electron / Q000379:methods; D009362:Neoplasm Metastasis / Q000473:pathology / Q000503:physiopathology*; D012516:Osteosarcoma / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D051381:Rats; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins
D003470:Culture Media; D004273:DNA, Neoplasm; D037102:Lectins