Cancer Stem Cells
Version of Record online: 22 MAY 2013
Copyright © 2013 AlphaMed Press
Volume 31, Issue 6, pages 1075–1085, June 2013
How to Cite
Ruiz-Ontañon, P., Orgaz, J. L., Aldaz, B., Elosegui-Artola, A., Martino, J., Berciano, M. T., Montero, J. A., Grande, L., Nogueira, L., Diaz-Moralli, S., Esparís-Ogando, A., Vazquez-Barquero, A., Lafarga, M., Pandiella, A., Cascante, M., Segura, V., Martinez-Climent, J. A., Sanz-Moreno, V. and Fernandez-Luna, J. L. (2013), Cellular Plasticity Confers Migratory and Invasive Advantages to a Population of Glioblastoma-Initiating Cells that Infiltrate Peritumoral Tissue. STEM CELLS, 31: 1075–1085. doi: 10.1002/stem.1349
Author contributions: P.R.-O.: collection of data and data analysis and interpretation; J.L.O.: collection of data and provision of study material; B.A., A.E.-A., M.T.B., J.A.M., L.G., L.N., S.D., and A.E.-O.: collection of data; J.M. and A.V.-B.: collection of data and provision of study patients; M.L., A.P., J.A.M.-C., and M.C.: data analysis and interpretation; V.S.: assembly of data; V.S.-M.: conception and design and data analysis and interpretation; J.L.F.-L.: conception and design, data analysis and interpretation, and manuscript writing.
Disclosure of potential conflicts of interest is found at the end of this article.
first published online in STEM CELLS EXPRESS February 8, 2013.
- Issue online: 22 MAY 2013
- Version of Record online: 22 MAY 2013
- Accepted manuscript online: 8 FEB 2013 09:25PM EST
- Manuscript Accepted: 19 JAN 2013
- Manuscript Received: 19 NOV 2012
- Instituto de Salud Carlos III (ISCIII)
- Spanish Ministry of Science and Innovation. Grant Numbers: PI10/02002, BFU2011-23983
- Red Temática de Investigación Cooperativa en Cáncer (RTICC). Grant Numbers: RD06/0020/0074, RD06/0020/0041, RD06/0020/0088, RD06/0020/0046
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Grant Number: CB06/05/0037
- Instituto de Formacion e Investigacion Marques de Valdecilla (IFIMAV). Grant Number: API2011-04
- Victoria Sanz-Moreno is a Cancer Research U.K. (CRUK). Grant Number: C33043/A12065
Additional Supporting Information may be found in the online version of this article.
|sc-12-1092_sm_SupplFigure1.tif||1347K||Figure S1. Differentiation capacity of TM and PT GICs. GICs formed neurospheres in culture. Neurosphere diameter after 7 days of culture was 160±32 μm in TM neurospheres and 73±15 μm in PT neurospheres (p<0.0001). Scale bar: 100 μm. Following neurosphere dissociation, individual cells, which stained positive for Sox2 (Scale bar: 10 μm), underwent astrocytic and neuronal differentiation in the presence of serum as determined by immunofluorescence with anti-GFAP and anti-Tuj1 antibodies respectively (Scale bar: 50 μm).|
|sc-12-1092_sm_SupplFigure2.tif||1297K||Figure S2. Patterns of cell invasion in neurosphere cultures. (A), (B), Neurospheres containing TM or PT cells were embedded in collagen matrices and the radial invasion of the matrix by tumour cells was visualized by light microscopy. Individual invasion, I, was determined by the mean distance from the edge of the neurosphere to the most distant migrating cells, whereas collective invasion, C, was quantitated by measuring the area between the edge of the neurosphere and the front of migrated cells. Histograms represent the mean±SD of three independent experiments. *p<0.005. (C), TM and PT cells migrating away from the neurospheres. Note the collective strands of invading PT cells (arrow). Scale bar: 10 μm.|
|sc-12-1092_sm_SupplFigure3.tif||2542K||Figure S3. In vivo association of PT cells to blood vessels. (A), Electron micrographs of semithin sections from the brain of mice xenografted with GICs. Arrows indicate tumour cells and asterisks indicate blood vessels. Scale bar: 3 μm. (B), Confocal microscopy of tissue sections showing colocalization of fluorescence signals from PT cells (CherryFP) and endothelial cells (Lectin). Scale bar: 10 μm. (C), (D), CFSElabeled tumor cells were cultured on a monolayer of HUVEC endothelial cells, and tumor cells from F1 (non-adherent and poorly-adherent cells) and F2 (strongly-adherent cells) fractions were counted by flow cytometry. *p<0.001. (E), Representative fluorescence image showing the morphology of TM and PT cells cocultured with HUVEC. Scale bar: 100 μm.|
|sc-12-1092_sm_SupplvideoS1.avi||3407K||Video S1. Tracking of TM cells cultured on 1.5 kPa polyacrylamide matrix (Scale bar: 50 μm).|
|sc-12-1092_sm_SupplvideoS2.avi||5216K||Video S2. Tracking of PT cells cultured on 1.5 kPa polyacrylamide matrix (Scale bar: 50 μm).|
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