|
| Status |
Public on Jul 16, 2020 |
| Title |
Single-cell atlas of human leptomeningeal metastasis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The tumor microenvironment plays a critical regulatory role in cancer progression, especially in metastases to the central nervous system. Cancer cells inhabiting the cerebrospinal spinal fluid (CSF)-filled leptomeningeal space face substantial microenvironmental challenges including inflammation and sparse extracellular iron. Unlike CSF leukocytes, we find that cancer cells within the CSF express the iron-binding protein LCN2 and its receptor SCL22A17. Employing mouse models of LM, we find that the LCN2/SLC22A17 system is necessary to support leptomeningeal cancer cell growth. We find that infiltrating CSF macrophages generate inflammatory cytokines that induce cancer cell LCN2 expression. This LCN2/SLC22A17 system provides cancer cells superior access to limiting extracellular iron, allowing LCN2-expressing cancer cells to outcompete CSF macrophages for this resource. Finally, pharmacologic interruption of these interactions prevents cancer cell growth within the leptomeninges.
|
| |
|
| Overall design |
10x single-cell RNA-sequencing of human leptomeningeal metastasis
|
| |
|
| Contributor(s) |
Chi Y, Remsik J, Kiseliovas V, Pe'er D, Mazutis L, Boire A |
| Citation(s) |
32675368 |
| |
| Submission date |
May 15, 2020 |
| Last update date |
Jul 20, 2020 |
| Contact name |
Jan Remsik |
| E-mail(s) |
jan.remsik@vib.be
|
| Organization name |
VIB
|
| Department |
Center for Cancer Biology
|
| Street address |
Campus Gasthuisberg, Herestraat 49
|
| City |
Leuven |
| ZIP/Postal code |
3000 |
| Country |
Belgium |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (5)
|
|
| This SubSeries is part of SuperSeries: |
| GSE150681 |
Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis |
|
| Relations |
| BioProject |
PRJNA633130 |
| SRA |
SRP261871 |
Less...
More...