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| Status |
Public on Dec 10, 2015 |
| Title |
Transient activation of the WNT pathway after disruption/remodeling of colorectal cancer cell clusters promotes a malignant phenotype |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Cancer progression and wound healing share some characteristics. Most colorectal cancers are differentiated adenocarcinomas that maintain three-dimensional structures to some extent. Hence, disruption of the architecture can provoke remodeling similar to the remodeling of normal intestinal epithelium. We used our recently developed three-dimensional culture system to investigate the response of cancer cell spheroids to mechanical disruption. Specifically, we developed a protocol for homogenous disruption of the spheroids that maintained the cell-cell contacts. After disruption, 9 spheroids from 9 patient samples reformed within a few hours, and 2 showed accelerated spheroid growth. Stemness increased after spheroid disruption, as assessed by marker expression, spheroid forming capacity, radiation sensitivity, and tumorigenesis. The spheroid-forming capacity increased in 6 of 11 spheroids. The disruption signature, as determined by gene expression profiling, supported the incidence of remodeling and predicted the prognosis of the colorectal cancer patients. WNT and HER3 signaling was increased in the reformed spheroids, and suppression of these signaling pathways attenuated the increases in growth and stemness after disruption. Thus, disorganized architecture in patient tumors might reflect the processes of disruption and subsequent remodeling and represent a cause rather than simply a consequence of malignancy progression.
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| Overall design |
Gene expression in cancer tissue-originated spheroids (CTOSs) was measured at pre, 6 hr, 24 hr, and 4 days after mechanical disruption. One experiment was performed at each time point.
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| Contributor(s) |
Inoue M |
| Citation(s) |
29662620 |
| Submission date |
Dec 09, 2015 |
| Last update date |
Mar 23, 2021 |
| Contact name |
Masahiro Inoue |
| E-mail(s) |
masa_inoue@kuhp.kyoto-u.ac.jp
|
| Organization name |
Kyoto Univ Graduate School of Medicine
|
| Department |
Clinical Bio-resource Research and Development
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| Street address |
Med-Pharm Collaboration Bldg 503, Shimoadachi-cho 46, Sakyou-ku, Kyoto, 606-8304, Japan
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| City |
Kyoto |
| State/province |
Kyoto |
| ZIP/Postal code |
606-8304 |
| Country |
Japan |
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| Platforms (1) |
| GPL13607 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA305551 |
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