Investigation of Interaction between SAOS-2 Osteosarcoma Cells and Endothelium

Eylul F. ERGUVEN – Bela Schwartz Fellow, Faculty of Dentistry, The University of Sydney

Summary

Because vascular endothelial cells form the critical barrier that must be breached by malignant tumour cells to spread via blood, it is of particular interest to understand interactions between endothelium and malignant cells. Earlier studies in this laboratory determined that cultured SAOS-2 osteosarcoma cells induce apoptosis, which is a form of cellular suicide, in cultured endothelium. This 'touch of death' phenomenon may play an important role in providing access to the blood by spreading malignant cells, but we have since discovered a further separate interaction between these SAOS-2 cells and fibroblasts, in which the fibroblasts and malignant cells exchange components of plasma membrane and cytoplasm, rather than there being an apoptotic response akin to that which we had earlier seen in endothelium.
The current project thus focused on determining if that in addition to the 'touch of death' for endothelium, SAOS-2 might also share membrane and cytoplasm with the endothelial cells they contact. This work supported by the Bela Schwartz Fellowship, has revealed surprisingly extensive sharing of not only membrane and cytoplasm between co-cultured SAOS-2 and endothelium, but also the uptake of endothelial nuclear material by SAOS-2. This may help account for the phenomenon of 'vascular mimicry' reported for some tumours, in which tumour cells mimic blood vessels and plumb themselves into the systemic circulation. In addition, it was discovered that the tumour cells induce highly directional secretion of inflammatory cytokines from endothelium, together with altered matrix metalloproteinase production. These observations, together with the earlier defined apoptotic response, reveal much more complex interactions between endothelium and osteosarcoma cells than had been previously supposed, and compel re-evaluation of the current model for tumour development.