Abstract for presentation at 13th International Congress on Oral Pathology and Medicine

Contact induced apoptosis of stromal cells by malignant tumour cells: a previously unrecognised mechanism for tumour invasion

  • M Huynh, Cellular and Molecular Pathology Research Unit, Discipline of Oral Pathology and Oral Medicine, Australia
  • A McEwan, Cellular and Molecular Pathology Research Unit, Discipline of Oral Pathology and Oral Medicine, Australia
  • C Emmanuel, Cellular and Molecular Pathology Research Unit, Discipline of Oral Pathology and Oral Medicine, Australia
  • H Medbury, Cellular and Molecular Pathology Research Unit, Discipline of Oral Pathology and Oral Medicine, Australia
  • A Leick, Cellular and Molecular Pathology Research Unit, Discipline of Oral Pathology and Oral Medicine, Australia
  • Murray Walker, Cellular and Molecular Pathology Research Unit, Discipline of Oral Pathology and Oral Medicine, United Kingdom
  • Hans Zoellner, University of Sydney, Australia

    • Purpose: We recently described a contact dependent pro-apoptotic activity in malignant tumour cells for vascular endothelium, indicating a possible role for this in metastasis (J Pathol 2003, 201:395-403). This study was to investigate the further possibility that a similar contact dependent activity may also contribute to tumour invasion separate to metastasis by induction of apoptosis in fibroblasts and smooth muscle cells.
    Results: Human gingival fibroblasts (HGF), human tenons fibroblasts (HTF) and human umbilical artery smooth muscle cells (SMC) were co-cultured with SAOS-2 osteosarcoma cells and the survival of stromal cells monitored over time. Similar to earlier observations in endothelium, all stromal cell types reduced significantly in number during co-culture with SAOS-2 (p < 0.05). DNA gel electrophoresis indicates reduced stromal cell number was due to apoptosis. Apoptosis was not due to soluble factors, as tumour cell conditioned medium did not affect stromal cell number. Preliminary data with human colon carcinoma cells (SW480) indicate a similar activity. FACS analysis revealed Fas and Fas ligand are present on stromal and tumour cells, respectively. SMC Fas was functional as demonstrated by agonistic antibody CH11, however, blocking Fas with antagonistic antibody ZB4 did not inhibit stromal cell death. A non-caspase dependent apoptotic pathway, perhaps involving calpains or cathepsins may be involved because inhibition of caspase by Z-VAD-FMK had no effect. Experiments continue characterizing the activity, and also SAOS-2 transfected with green-fluorescent protein to investigate events in-vivo.
    Conclusions: Contact dependent induction of stromal cell apoptosis by malignant tumour cells may contribute significantly to tumour invasion, and this may be by non-caspase dependent mechanisms for induction of apoptosis. This raises the possibility for development of novel strategies for the management of invasive tumours.

    Conference Organiser - ICMS Pty Ltd