[Frontiers in Bioscience 14, 3085-3093, January 1, 2009]

Novel shear flow assay provides evidence for non-linear modulation of cancer invasion

Samuel Hagglund1, Andreas Hoppe1, Deborah Aubyn2, Tamara Cavanna2, Peter Jordan2, Daniel Zicha2

1Kingston University, Digital Imaging Research Centre, Penrhyn Rd, Kingston-upon-Thames KT1 2EE, UK, 2Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3PX, UK

TABLE OF CONTENT

1. Abstract
2. Introduction
3. Materials and methods
3.1. Cell culture
3.2. Cell labelling
3.3. Flow chamber
3.4. Microscopy and image acquisition
3.5. Image-processing-based quantitative analysis of invasion
4. Results
4.1. Novel flow chamber assay with image-processing-based measurements designed for studying the dynamics of the invasion of sarcoma cells into monolayers of endothelial cells
4.2. Metastatic sarcoma cells invade the monolayer of endothelial cells by opening gaps between endothelial cells while non metastatic sarcoma cells do not
4.3. The initial invasion rate of the metastatic cells is enhanced by shear flow while later the cells without shear stress achieve higher levels of invasion
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

Cancer is a frequent disease in western countries and there is no effective treatment for metastasis, the main cause of death in cancer patients. The situation can be improved by a better understanding of the cancer invasion process. In order to reveal new aspects of this dynamic process, we developed a novel direct viewing cancer cell invasion assay with shear flow in vitro. This assay comprised of a custom-made flow chamber, specially developed cell labelling, high-resolution wide-field microscopy and image-processing-based quantitation. We applied this assay to metastatic rat sarcoma cells which invaded monolayers of rat endothelial cells. Our findings showed that after adhesion, the sarcoma cells initially invaded significantly faster under flow conditions compared to situations without shear stress. Later, however, the rate of invasion under flow decreased and the sarcoma cells without shear stress achieved significantly higher levels of invasion. Our observations thus revealed the non-linear modulation of a cancer cell invasion process by shear flow, demonstrating that cancer cells can respond to flow by enhancement of invasiveness similarly to white blood cells.