Speaker
Dr
Jeffrey Crosbie
(University of Melbourne)
Description
A novel, synchrotron-based approach, known as microbeam radiotherapy (MRT) has the potential to revolutionise the way radiotherapy is performed. MRT uses a lattice of kilovoltage X-ray microbeamlets, with each beamlet being 10-50 microns wide with centre-to-centre separation of 100-300 microns. It is not known why normal tissues can tolerate such high doses of radiation, or why tumor response to MRT is so effective when only a fraction of their volume is irradiated by the lattice of microbeams. Our group previously showed that tumor cells showed extensive migration within 24 hours post-MRT. By contrast, in normal skin, peak dose-irradiated cells showed minimal evidence of migration up to 3.5 days post irradiation. The rapid intermixing of lethally irradiated cells with undamaged cells within the tumor may accentuate cell-mediated communication, thus providing a plausible explanation for the effectiveness of MRT despite the fact that less than half the cells in the tumor are lethally irradiated by the lattice of X-rays. The aim of the project is to investigate how cell migration is influenced by MRT and conventional radiation. We use time-lapse microscopy (live cell imaging) coupled with sophisticated image processing techniques to track individual cells within the well chamber slides. Briefly, we irradiate well chamber slides containing cultured normal and malignant cells with a range of doses using a conventional Co-60 radiation source and on the Imaging & Medical Beamline at the Australian Synchrotron in Melbourne. We cultured cells in high and low density conditions to investigate migration across wounds (confluent cells) and for quasi-isolated cells. Preliminary statistical analysis of the data suggests that while the averaged displacement of cells may not vary significantly when cells are irradiated with doses of 2, 5, or 10 Gy of conventional radiation; the higher doses caused an increase in the variance of cell displacements. Preliminary synchrotron MRT experiments have shown increasing doses causing increasing migration speed. However the synchrotron MRT experiments suffered from unknown dosimetry and more precise experiments are required. The quantitative cell migration data we will generate will provide new and novel insights into basic tumour biology and will deepen our understanding of cell migration in the presence of ionising radiation.
Primary author
Dr
Jeffrey Crosbie
(University of Melbourne)
Co-authors
Dr
Camden Lo
(Monash University)
Mr
Cameron Nowell
(Ludwig Institute of Cancer Research)
Prof.
Fima Klebaner
(Monash University)
Prof.
Kais Hamza
(Monash University)
Mr
Mohammed-Johari Ibahim
(University of Melbourne)
Prof.
Peter Rogers
(University of Melbourne)
Ms
Rotem Aharon
(Monash University)
