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| Status |
Public on May 04, 2023 |
| Title |
Epiploic Adipose Tissue (EPAT) in Obese Individuals Promotes Colonic Tumorigenesis: A Novel Model for EPAT-Dependent Colorectal Cancer Progression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The obesity epidemic is associated with increased colorectal cancer (CRC) risk and progression, the mechanisms of which remain unclear. In obese individuals, hypertrophic epiploic adipose tissue (EPAT), attached to the colon, has unique characteristics compared to other fats. We hypothesized that this understudied fat could serve as a tumor-promoting tissue and developed a novel microphysiological system (MPS) for human EPAT-dependent colorectal cancer (CRC-MPS). In CRC-MPS, obese EPAT, unlike lean EPAT, considerably attracted colon cancer HT29-GFP cells and enhanced their growth. Conditioned media (CM) from the obese CRC-MPS significantly increased the growth and migration of HT29 and HCT116 cells (p< 0.001). In HT29 cells, CM stimulated differential gene expression (hOEC867) linked to cancer, tumor morphology, and metabolism similar to those in the colon of high-fat-diet obese mice. The hOEC867signature represented pathways found in human colon cancer. In unsupervised clustering, hOEC867separated transcriptomes of colon cancer samples from normal with high significance (PCA,p =9.6 × 10−11). These genes, validated in CM-treated HT29 cells (p< 0.05), regulate the cell cycle, cancer stem cells, methylation, and metastasis, and are similarly altered in human colon cancer (TCGA). These findings highlight a tumor-promoting role of EPAT in CRC facilitated with obesity and establishes a platform to explore critical mechanisms and develop effective treatments.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for HT29 cells treated with conditioned media from ESC-only MPS and obese EPAT MPS
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| Contributor(s) |
Iftikhar R, Snarski P, King AN, Ghimire J, Ruiz E, Lau F, Savkovic SD |
| Citation(s) |
36765934 |
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| Submission date |
Mar 29, 2023 |
| Last update date |
May 04, 2023 |
| Contact name |
Suzana Savkovic |
| E-mail(s) |
[email protected]
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| Phone |
7087900392
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| Organization name |
Tulane University
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| Department |
Pathology & Laboratory Medicine
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| Street address |
1430 Tulane Ave
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| City |
New Orleans |
| State/province |
LA |
| ZIP/Postal code |
70112 |
| Country |
USA |
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| Platforms (1) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA950126 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE228532_HT29_ASC-Con-CM_vs_HT29_Con.summary.genes-P_0.05.xlsx |
2.3 Mb |
(ftp)(http) |
XLSX |
| GSE228532_HT29_ASC-Con-CM_vs_HT29_SWAT-Con-CM.summary.genes_p0.05.xlsx |
1.4 Mb |
(ftp)(http) |
XLSX |
| GSE228532_HT29_Con_vs_HT29_SWAT-Con-CM.summary.genes_p0.05.xlsx |
2.4 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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