Computer-assisted quantification of motile and invasive capabilities of cancer cells.
High-throughput analysis of cancer cell dissemination and its control by extrinsic and intrinsic cellular factors is hampered by the lack of adequate and efficient analytical tools for quantifying cell motility. Oncology research would greatly benefit from such a methodology that allows to rapidly determine the motile behaviour of cancer cells under different environmental conditions, including inside three-dimensional matrices. We combined automated microscopy imaging of two- and three-dimensional cell cultures with computational image analysis into a single assay platform for studying cell dissemination in high-throughput. We have validated this new approach for medulloblastoma, a metastatic paediatric brain tumour, in combination with the activation of growth factor signalling pathways with established pro-migratory functions. The platform enabled the detection of primary tumour and patient-derived xenograft cell sensitivity to growth factor-dependent motility and dissemination and identified tumour subgroup-specific responses to selected growth factors of excellent diagnostic value.
Department of Oncology, Children's Research Center, University Children's Hospital Zürich, August-Forel Strasse 1, CH-8008 Zürich, Switzerland.
Karthiga Santhana
KS
Kumar
Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 4, CH-8093 Zürich, Switzerland.
Max
M
Pillong
Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 4, CH-8093 Zürich, Switzerland.
Jens
J
Kunze
Department of Neurology, University Hospital Zürich and University of Zürich, Frauenklinikstrasse 26, CH-8091 Zürich, Switzerland.
Isabel
I
Burghardt
Department of Neurology, University Hospital Zürich and University of Zürich, Frauenklinikstrasse 26, CH-8091 Zürich, Switzerland.
Michael
M
Weller
Department of Oncology, Children's Research Center, University Children's Hospital Zürich, August-Forel Strasse 1, CH-8008 Zürich, Switzerland.|Department of Oncology, University Children's Hospital Zürich, Steinwiesstrasse 75, CH-8032 Zürich, Switzerland.
Michael A
MA
Grotzer
Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 4, CH-8093 Zürich, Switzerland.
Gisbert
G
Schneider
Department of Oncology, Children's Research Center, University Children's Hospital Zürich, August-Forel Strasse 1, CH-8008 Zürich, Switzerland.
Martin
M
Baumgartner
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008527:Medulloblastoma / Q000235:genetics / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics; D012984:Software; D059016:Tumor Microenvironment / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D036341:Intercellular Signaling Peptides and Proteins