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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 20, 2024 |
| Title |
Endothelial Pim3 kinase protects the vascular barrier during lung metastasis (set2) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Endothelial cells (ECs) form a tissue-specific barrier for disseminating cancer cells in distant organs. However, the molecular regulation of the ECs in the metastatic niche is poorly understood. Here, we analyzed the transcriptional reprogramming of ECs in the lung metastatic niche six hours after the arrival of melanoma cells in the niche. We discovered a novel EC cluster derived from venous capillaries in response to infiltrating cancer cells, which was enriched for cell-cell communication pathways, including the Dll4, Vegf and Il6-Jak-Stat pathways. The Jak-Stat activated oncogenic Pim3 kinase was a marker of the cancer responding ECs, being upregulated in spontaneous metastasis models and in ECs of human cancer. Notably, PIM inhibition increased vascular leakage and metastatic colonization in vivo and impaired the EC barrier via decreased junctional Cadherin-5 and catenins a, b and d. Thus, PIM3 protects the EC barrier in the metastatic niche, which may impair the efficacy of PIM inhibitors in cancer therapies.
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| Overall design |
To investigate transcriptome changes of endothelial cells during metastatic colonization, we isolated endothelial cells for scRNASeq from lungs of healthy mice and 6 hours after B16F10 cell injection into C57BL/6 mice via tail vein
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| Contributor(s) |
Santio N, Ganesh K, Kaipainen P, Halme A, Saharinen P |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jan 19, 2024 |
| Last update date |
Sep 20, 2024 |
| Contact name |
Niina M Santio |
| E-mail(s) |
niina.santio@utu.fi
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| Organization name |
University of Helsinki
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| Street address |
Haartmaninkatu 8
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| City |
Helsinki |
| ZIP/Postal code |
00290 |
| Country |
Finland |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA1066871 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE253749_RAW.tar |
616.4 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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