 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 20, 2020 |
| Title |
Endothelial stromal cells enhance lung-tumor cell migration through TNFα and SDF-1α secretion |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Recent studies have noted the tumor-stroma interaction as an integral part of tumor growth and spread as well as novel avenues for effective treatment. However, the details by which tumor and stroma cells communicate remain poorly understood. Here we show that the migration speed of the non-small-cell lung tumor cell line H838 is significantly increased under the influence of human pulmonary endothelial cells, HPAEC, in a transfilter co-culture system. To elucidate the effect of cell communication on the increased tumor cell migration, we record the H838 transcriptome response after the induction of migration in a hetero- and homogenous co-culture conditions. Gene Set enrichment analysis indicates a migration response of H838 in heterogenous co-culture system. Moreover, computationally transcription factor analysis relates the specific gene expression response to the cytokine-induced up-stream receptor activity and subsequently linking these factors to the upstream receptors via shortest paths across a directed protein-protein interaction network. This analysis predicted TNF- and SDF-1 signaling as well as multiple receptors upstream of Stat3 as putative mediators of the transcriptome response. To close the signaling information path from transcription factors to the possible receptor activation, we determine secretome quantification using a cytokine array. The latter revealed the predicted TNFa, SDF-1a signaling molecules as well as other known migration cytokines, like IL8 and IL6, as possible candidates for increased migration. Addition through the recombinant proteins or respected inhibitions reveal TNFa as well as SDF-1a as an immediate and early-late secreted factors that cause the increase in H838 migration. Interestingly, both factors were not regulated on the gene level of the H838 in heterogenous co-culture conditions, consequential HPAEC produce TNFa and SDF1a as shown by qPCR technique. Concluding, our combined computational and experimental approach revealed a holistic overview on the migration enhancement of lung tumor cells due to endothelial derived factors. Increase in migration is caused by an early TNFa induced inflammation response followed by a SDF-1a activity to sustaining the phenotype of migration. This tumor-endothelial-communication give a new insight for tumor migration.
|
| |
|
| Overall design |
The human NSCLC cell line H838 was propagated in DMEM with 10% fetal calf serum and 50,000 U/ml Penicillin/Streptomycin. HPAEC was propagated in Endothelial cell growth medium 2 (Promocell) including 2% fetal calf serum with supplements. H838 and HPAEC cells were applied to polycarbonate transwell culture inserts. The filters were placed to the corresponding well plates and allowed to propagate until confluence was reached. H838 cells were cultivated together with HPAEC cells (heteroenous co-culture) or together with the same h838 cell line (homogenous co-culture) serving as controls. Confluent H838 monolayers from wither the heterogenous or homogenous transfilter system were scratched multiple times to induce tumor cell migration. H838 cells were lysed at time points 0, 0.5, 1, 2, 3, 4, 5, 10, 15 and 24 hours after scratching. The samples at 0 and 24 hours were taken in duplicates.
|
| |
|
| Contributor(s) |
Busch H, Bao J, Dauscher D, Boerries M, Depner S, Müller M |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Nov 06, 2012 |
| Last update date |
Aug 20, 2020 |
| Contact name |
Hauke Busch |
| E-mail(s) |
hauke.busch@uni-luebeck.de
|
| Phone |
+49-451-3101-8470
|
| Organization name |
University of Lübeck
|
| Department |
Lübeck Institute of Experimental Dermatology
|
| Street address |
Ratzeburger Allee 160
|
| City |
Lübeck |
| State/province |
Schleswig-Holstein |
| ZIP/Postal code |
23538 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
|
| Samples (24)
|
|
| Relations |
| BioProject |
PRJNA179082 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE42076_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| GSE42076_non-normalized.txt.gz |
6.9 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...