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| Status |
Public on May 21, 2023 |
| Title |
Extracellular acidosis promotes colonization of lung metastases by mediating extracellular matrix remodeling and vasculogenic mimicry |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Acidosis is a hallmark of the tumor microenvironment caused by the metabolic switch from glucose oxidative phosphorylation to glycolysis. It has been largely associated with tumor growth and progression, nevertheless, how acidosis promotes metastatic dissemination remains largely unknown.
In this study, we established a long-term acidosis model using patient-derived lung cancer cells. By comparing xenograft inoculates at the cluster sizes of lung cancer circulating tumor cells, the acidosis cells display significantly higher incidence of secondary tumor establishment than their neutral pH counterparts.
Transcriptomics analyses reveal a profound remodeling of the extracellular matrix in the acidosis cells, featuring the upregulation of ITGA4 and HAS3 genes, In clinical specimen, overexpression of both ITGA4 and HAS3 proteins are associated with primary tumors with metastatic ability, and their distribution is markedly accentuated around vascular mimicry structures in secondary tumors.
We show that acidosis cells display higher ability of vascular mimicry in vitro, and are enriched in ABC transporter-dependent side population cells.
Our data support that acidosis drives tumor metastatic colonization via enhanced extracellular matrix remodeling and vascular mimicry. Assessment on the prognostic value of tumor acidosis for metastasis and possible treatment directions are discussed.
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| Overall design |
This submission contains RNA-Seq data of transcriptome analysis of CLS1 cells under the tratments of long-term pH6.6 culture, long-term pH7.4 control, 24hrs pH6.6 culture, and 0hr control.
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| Contributor(s) |
Shie W |
| Citation(s) |
37888615 |
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| Submission date |
Apr 10, 2022 |
| Last update date |
Dec 01, 2023 |
| Contact name |
Wan-Yi Shie |
| E-mail(s) |
sun24935@gmail.com
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| Organization name |
National Taiwan University
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| Street address |
No.1, Changde St., Jhongjheng District, Taipei City 100, Taiwan R.O.C.
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| City |
Taipei |
| ZIP/Postal code |
886 |
| Country |
Taiwan |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (10)
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| GSM6037580 |
CLS1, pH7.4, rep 2, exp 1 |
| GSM6037581 |
CLS1, pH6.6, rep 1, exp 2 |
| GSM6037582 |
CLS1, pH6.6, rep 2, exp 2 |
| GSM6037583 |
CLS1, pH7.4, rep 1, exp 2 |
| GSM6037584 |
CLS1, pH7.4, rep 2, exp 2 |
| GSM6037585 |
CLS1, pH6.6, 24H |
| GSM6037586 |
CLS1, 0H |
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| Relations |
| BioProject |
PRJNA825255 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE200546_RAW.tar |
4.2 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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