|
|
GEO help: Mouse over screen elements for information. |
|
Status |
Public on Oct 01, 2020 |
Title |
Using a xenograft model and RNA-seq to differentiate between the tumour and tumour microenvironment transcriptome |
Organisms |
Homo sapiens; Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
In addition to the tumour cells, breast tumours contain other cell types such as fibroblasts, adipocytes, inflammatory and immune cells. Together with the extracellular matrix, these non-tumour cells compose the tumour microenvironment (TME). Complex interactions occur between tumour cells and the TME that can inhibit or stimulate tumour cell growth, metastasis and/or chemoresistance. While treatment of tumours with chemotherapeutic agents such as Abraxane, leads to apoptosis of tumour cells, it can also have consequences for the cellular makeup and transcriptional profile of the TME and these, like the increased infiltration of macrophages, may have detrimental effects. Transcriptome profiling of whole tumours from mice injected with tumour cell lines and treated with combinations of chemotherapeutic drugs has provided novel insights into pathways affected by different agents and diagnostic signatures. However, differences in the cellular composition of tumours from treated mice can have confounding effects and increase variation in whole tumour transcriptomes. To be able to examine the effects of co-treatment of Abraxane with another drug, we performed RNA-seq on tumours from mice injected with the human breast cancer cell line MDA-MB-231. We then separated reads mapped to the human and mouse genomes in silico, creating tumour and TME transcriptomes for control, Abraxane, drug and combination treated mice. Separation of the tumour and TME profiles revealed that while in the tumour cells, co-addition of the drug potentiated Abraxane’s inhibitory effect on cell cycle genes and promotional effect on antigen presentation genes, in the TME it inhibited genes involved in the inflammation and migration responses and promoted genes involved in lipid and xenobiotic metabolism.
|
|
|
Overall design |
4 mice per treatment. 4 treatments. Paired end RNA-seq
|
|
|
Contributor(s) |
Hardy K, Tan A, Boulding T, Rao S |
Citation missing |
Has this study been published? Please login to update or notify GEO. |
|
Submission date |
Oct 11, 2018 |
Last update date |
Oct 01, 2020 |
Contact name |
Kristine Hardy |
E-mail(s) |
[email protected]
|
Organization name |
University of Canberra
|
Lab |
Cytokine Gene Expression
|
Street address |
University of Canberra
|
City |
Bruce |
State/province |
ACT |
ZIP/Postal code |
0200 |
Country |
Australia |
|
|
Platforms (1) |
GPL19415 |
Illumina NextSeq 500 (Homo sapiens; Mus musculus) |
|
Samples (16)
|
|
Relations |
BioProject |
PRJNA495798 |
SRA |
SRP165188 |
Supplementary file |
Size |
Download |
File type/resource |
GSE121119_gene_count_matrix_human.csv.gz |
874.4 Kb |
(ftp)(http) |
CSV |
GSE121119_gene_count_matrix_mouse.csv.gz |
708.2 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
|
|
|
|
|