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The Department of Biomedicine

CCBIO seminar: Ian Mackenzie

Stem cell plasticity in head and neck cancers

Ian Mackenzie
Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK

The presence of stem cells in malignancies has several implications for diagnosis and therapy. Typically, malignant change originates in stem cells, they are the drivers of tumour growth and, being more resistant to chemo- and radio-therapies, they are responsible for tumour recurrence after therapy. As "tumour initiating cells" they generate secondary growth but the mechanisms of their translocation to distant metastatic sites are unclear. An "epithelial to mesenchymal transition" (EMT) has been widely proposed but, despite EMT-like changes at tumour margins, individual migrating EMT cells are difficult to identify in human tissues. A further reversible transition to an "amoeboid" cell type has now been studied. Isolation and analysis of amoeboid cells indicate that they lack expression of markers typically used to identify EMT cells (e.g. keratins, ESA, e-cadherin, CD24) and this probably renders them "invisible". However, some genes are found to be selectively expressed in amoeboid cells and staining for such gene products identifies cells in the stroma adjacent to human tumours. It appears that stem cells are present in at least three different forms in head and neck squamous cell carcinoma (HNSCC) and that the plasticity of these cells markedly influences tumour properties and therapeutic responses.

Chairperson: Anne Christine Johannessen, CCBIO