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Series GSE10096 Query DataSets for GSE10096
Status Public on Feb 15, 2008
Title A novel lung cancer gene signature mediates metastatic bone colonization by a dual mechanism
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and a dismal prognosis. To identify and functionally characterize genes involved in the mechanisms of osseous metastasis we developed a murine lung cancer model. Comparative transcriptomic analysis identified genes encoding signaling molecules (such as TCF4 and PRKD3), and cell anchorage related proteins (MCAM, and SUSD5), some of which were basally modulated by TGFbeta in tumor cells and in conditions mimicking tumor-stroma interactions. Triple gene combinations induced not only high osteoclastogenic activity but also a marked enhancement of global metalloproteolytic activities in vitro. These effects were strongly associated with robust bone colonization in vivo, whereas this gene subset was ineffective in promoting local tumor growth and cell homing activity to bone. Interestingly, global inhibition of metalloproteolytic activities and simultaneous TGFbeta blockade in vivo led to increased survival and a remarkable attenuation of bone tumor burden and osteolytic metastasis. Thus, this metastatic gene signature mediates bone-matrix degradation by a dual mechanism of induction of TGFbeta-dependent osteoclastogenic bone resorption and enhancement of stroma-dependent metalloproteolytic activities. Our findings suggest the cooperative contribution of host-derived and cell-autonomous effects directed by a small subset of genes in mediating aggressive osseous colonization.
Keywords: disease state analysis of human metastatic cell lines
Overall design Human highly metastatic cell lines derived from Non-Small Cell Lung Carcinoma (NSCLC) with specific bone tropism. Cell lines were selected by induction of prominent bone metastases lesions. The metastatic lines were systematically and accurately discriminate using 3 complementary parameters: survival curves of newly injected mice; computerized image analysis of bone metastatic areas; conspicuous SCCs derived from each animal (10 mice/group).
Genome-wide expression analysis was done using 13 microarrays, corresponding to 4 samples of control non-metastatic cell lines and 9 samples of 3 different highly metastatic cell lines (M1, M4, M5) each with 3 biological replicates. Moreover, in each microarray pools of 3 groups of the corresponding cells were used.
Contributor(s) Lecanda F, De Las Rivas J, Dotor J, Borras-Cuesta F, Garcia-Tuñon I, Anton I, Luis-Ravelo D, Vicent S
Citation(s) 18381434
Submission date Jan 07, 2008
Last update date Dec 06, 2018
Contact name Javier De Las Rivas
Phone 34 923 294819
Organization name Cancer Research Center (CiC-IBMCC)
Department CSIC and University of Salamanca
Lab Bioinformatics and Functional Genomics
Street address Campus Miguel de Unamuno
City Salamanca
ZIP/Postal code 37001
Country Spain
Platforms (1)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (13)
GSM254984 Lung cancer metastatic gene signature: control cell lines without luciferase reporter, bio-replicate 1.
GSM254986 Lung cancer metastatic gene signature: control cell lines with luciferase reporter, bio-replicate 1.
GSM254987 Lung cancer metastatic gene signature: control cell lines without luciferase reporter, bio-replicate 2.
BioProject PRJNA108271

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Supplementary file Size Download File type/resource
GSE10096_RAW.tar 46.5 Mb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file

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