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Series GSE19426 Query DataSets for GSE19426
Status Public on Dec 06, 2010
Title Comprehensive Characterization of 3D Models for Prostate Cancer Growth and Invasion in Laminin-rich Extracellular Matrix
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Full title: Comprehensive Characterization of Three-Dimensional Models for Prostate Cancer Growth and Invasion in Laminin-rich Extracellular Matrix
Prostate Cancer (PrCa) cells undergo acinar morphogenesis and spheroid formation in three-dimensional (3D) culture, supported by laminin-rich extracellular matrix (lrECM, Matrigel). We developed miniaturized 3D model systems that facilitate investigation of morphogenesis and invasion of normal and PrCa cell lines in lrECM. Primary and non-transformed cell lines formed round structures with strong cell-cell contacts and epithelial polarization, lumen and a complete basal lamina (BL). In contrast, most PrCa cell lines formed either defective, “mass” spheroids with incomplete BL, or invasive “stellate” structures. The bioinformatic analyses of genome-wide mRNA expression data revealed massive alteration of key functional and signaling pathways in 3D cultures, with lipid and steroid metabolism, epigenetic reprogramming, and differentiation-related transcription factors induced across all cell lines by lrECM. In invasive cells, AKT, PI3Kinase, mTOR, and hedgehog signaling pathways were most highly activated, validated by small molecule inhibitors compounds specifically targeting key regulatory molecules. Compounds against AKT and PI3kinase pathways were significantly more effective in invasive cells, compared to mass or round/normal phenotype spheroids, and monolayer culture. A severe morphologic conversion was observed in PC-3 and PC-3M cells, transforming initially round, normal-appearing epithelial spheroids into rapidly invading cell masses. Markers for EMT (epithelial-mesenchymal transition) were highly expressed already in early stage, round spheroids prior to invasive conversion, and were not further increased in invasive cells. This indicates that PrCa cells can display extraordinary plasticity. EMT may be involved in providing a metastable genotype that allows morphological transformation, but is not be required for invasive processes themselves.
 
Overall design Total RNA was obtained from non-transformed prostate epithelial cells and prostate cancer cells cultured in monolayer and three-dimensional laminin-rich extracellular matrix (growth factor-reduced Matrigel).
 
Contributor(s) Härmä V, Virtanen J, Mäkelä R, Happonen A, Mpdindi J, Knuuttila M, Kohonen P, Lötjönen J, Kallioniemi O, Nees M
Citation(s) 20454659
Submission date Dec 11, 2009
Last update date Mar 20, 2017
Contact name Matthias Nees
E-mail(s) matthias.nees@vtt.fi
Phone +358 40 8314 839
Fax +358 2 720 2840
URL http://www.vtt.fi
Organization name VTT Technical Research Centre of Finland
Department Medical Biotechnology
Street address Itäinen Pitkäkatu 4C
City Turku
ZIP/Postal code 20521
Country Finland
 
Platforms (1)
GPL6883 Illumina HumanRef-8 v3.0 expression beadchip
Samples (54)
GSM483220 PC-3 cells cultured in monolayer. Rep 1
GSM483221 PC-3 cells cultured in monolayer. Rep 2
GSM483222 PC-3 cells cultured 8 days in GFR Matrigel. Rep 1
Relations
BioProject PRJNA122291

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE19426_RAW.tar 3.9 Mb (http)(custom) TAR
GSE19426_non-normalized.txt.gz 8.0 Mb (ftp)(http) TXT
Processed data included within Sample table
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