Contact-dependent signaling triggers tumor-like proliferation of CCM3 knockout endothelial cells in co-culture with wild-type cells
dc.bibliographicCitation.firstPage | 340 | |
dc.bibliographicCitation.issue | 6 | |
dc.bibliographicCitation.journalTitle | Cellular and molecular life sciences : (CMLS) | eng |
dc.bibliographicCitation.volume | 79 | |
dc.contributor.author | Rath, Matthias | |
dc.contributor.author | Schwefel, Konrad | |
dc.contributor.author | Malinverno, Matteo | |
dc.contributor.author | Skowronek, Dariush | |
dc.contributor.author | Leopoldi, Alexandra | |
dc.contributor.author | Pilz, Robin A. | |
dc.contributor.author | Biedenweg, Doreen | |
dc.contributor.author | Bekeschus, Sander | |
dc.contributor.author | Penninger, Josef M. | |
dc.contributor.author | Dejana, Elisabetta | |
dc.contributor.author | Felbor, Ute | |
dc.date.accessioned | 2023-03-06T07:01:24Z | |
dc.date.available | 2023-03-06T07:01:24Z | |
dc.date.issued | 2022 | |
dc.description.abstract | Cerebral cavernous malformations (CCM) are low-flow vascular lesions prone to cause severe hemorrhage-associated neurological complications. Pathogenic germline variants in CCM1, CCM2, or CCM3 can be identified in nearly 100% of CCM patients with a positive family history. In line with the concept that tumor-like mechanisms are involved in CCM formation and growth, we here demonstrate an abnormally increased proliferation rate of CCM3-deficient endothelial cells in co-culture with wild-type cells and in mosaic human iPSC-derived vascular organoids. The observation that NSC59984, an anticancer drug, blocked the abnormal proliferation of mutant endothelial cells further supports this intriguing concept. Fluorescence-activated cell sorting and RNA sequencing revealed that co-culture induces upregulation of proangiogenic chemokine genes in wild-type endothelial cells. Furthermore, genes known to be significantly downregulated in CCM3−/− endothelial cell mono-cultures were upregulated back to normal levels in co-culture with wild-type cells. These results support the hypothesis that wild-type ECs facilitate the formation of a niche that promotes abnormal proliferation of mutant ECs. Thus, targeting the cancer-like features of CCMs is a promising new direction for drug development. | eng |
dc.description.version | publishedVersion | eng |
dc.identifier.uri | https://oa.tib.eu/renate/handle/123456789/11656 | |
dc.identifier.uri | http://dx.doi.org/10.34657/10689 | |
dc.language.iso | eng | |
dc.publisher | Cham (ZG) : Springer International Publishing AG | |
dc.relation.doi | https://doi.org/10.1007/s00018-022-04355-6 | |
dc.relation.essn | 1420-9071 | |
dc.relation.issn | 1420-682X | |
dc.rights.license | CC BY 4.0 Unported | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject.ddc | 570 | |
dc.subject.ddc | 610 | |
dc.subject.other | Cerebral cavernous malformations | eng |
dc.subject.other | Co-culture | eng |
dc.subject.other | CRISPR/Cas9 genome editing | eng |
dc.subject.other | NSC59984 | eng |
dc.subject.other | RNA sequencing | eng |
dc.subject.other | Tumor-like behavior | eng |
dc.title | Contact-dependent signaling triggers tumor-like proliferation of CCM3 knockout endothelial cells in co-culture with wild-type cells | eng |
dc.type | Article | eng |
dc.type | Text | eng |
tib.accessRights | openAccess | |
wgl.contributor | INP | |
wgl.subject | Medizin, Gesundheit | ger |
wgl.subject | Biowissenschaften/Biologie | ger |
wgl.type | Zeitschriftenartikel | ger |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- Contact-dependent_signaling_triggers_tumor-like_proliferation.pdf
- Size:
- 7.6 MB
- Format:
- Adobe Portable Document Format
- Description: