Sökning: onr:"swepub:oai:DiVA.org:uu-477777" >
Contact-dependent s...
Contact-dependent signaling triggers tumor-like proliferation of CCM3 knockout endothelial cells in co-culture with wild-type cells
-
- Rath, Matthias (författare)
- Univ Greifswald, Dept Human Genet, Univ Med Greifswald, Fleischmannstr 43, D-17475 Greifswald, Germany.;Univ Greifswald, Interfac Inst Genet & Funct Genom, Fleischmannstr 43, D-17475 Greifswald, Germany.
-
- Schwefel, Konrad (författare)
- Univ Greifswald, Dept Human Genet, Univ Med Greifswald, Fleischmannstr 43, D-17475 Greifswald, Germany.;Univ Greifswald, Interfac Inst Genet & Funct Genom, Fleischmannstr 43, D-17475 Greifswald, Germany.
-
- Malinverno, Matteo (författare)
- FIRC Inst Mol Oncol Fdn IFOM, Vasc Biol Unit, Milan, Italy.
-
visa fler...
-
- Skowronek, Dariush (författare)
- Univ Greifswald, Dept Human Genet, Univ Med Greifswald, Fleischmannstr 43, D-17475 Greifswald, Germany.;Univ Greifswald, Interfac Inst Genet & Funct Genom, Fleischmannstr 43, D-17475 Greifswald, Germany.
-
- Leopoldi, Alexandra (författare)
- Austrian Acad Sci, Inst Mol Biotechnol, Vienna, Austria.
-
- Pilz, Robin A. (författare)
- Univ Greifswald, Dept Human Genet, Univ Med Greifswald, Fleischmannstr 43, D-17475 Greifswald, Germany.;Univ Greifswald, Interfac Inst Genet & Funct Genom, Fleischmannstr 43, D-17475 Greifswald, Germany.
-
- Biedenweg, Doreen (författare)
- Univ Greifswald, Ctr Innovat Competence Humoral Immune React Cardi, Greifswald, Germany.
-
- Bekeschus, Sander (författare)
- Leibniz Inst Plasma Sci & Technol INP, ZIK Plasmatis, Greifswald, Germany.
-
- Penninger, Josef M. (författare)
- Austrian Acad Sci, Inst Mol Biotechnol, Vienna, Austria.;Univ British Columbia, Life Sci Inst, Dept Med Genet, Vancouver, BC, Canada.
-
- Dejana, Elisabetta (författare)
- Uppsala universitet,Vaskulärbiologi,FIRC Inst Mol Oncol Fdn IFOM, Vasc Biol Unit, Milan, Italy.
-
- Felbor, Ute (författare)
- Univ Greifswald, Dept Human Genet, Univ Med Greifswald, Fleischmannstr 43, D-17475 Greifswald, Germany.;Univ Greifswald, Interfac Inst Genet & Funct Genom, Fleischmannstr 43, D-17475 Greifswald, Germany.
-
visa färre...
-
Univ Greifswald, Dept Human Genet, Univ Med Greifswald, Fleischmannstr 43, D-17475 Greifswald, Germany;Univ Greifswald, Interfac Inst Genet & Funct Genom, Fleischmannstr 43, D-17475 Greifswald, Germany. FIRC Inst Mol Oncol Fdn IFOM, Vasc Biol Unit, Milan, Italy. (creator_code:org_t)
- 2022-06-04
- 2022
- Engelska.
-
Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer. - 1420-682X .- 1420-9071. ; 79:6
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://uu.diva-port... (primary) (Raw object)
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Nyckelord
- Cerebral cavernous malformations
- CRISPR
- Cas9 genome editing
- Tumor-like behavior
- NSC59984
- RNA sequencing
- Co-culture
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Rath, Matthias
-
Schwefel, Konrad
-
Malinverno, Matt ...
-
Skowronek, Dariu ...
-
Leopoldi, Alexan ...
-
Pilz, Robin A.
-
visa fler...
-
Biedenweg, Doree ...
-
Bekeschus, Sande ...
-
Penninger, Josef ...
-
Dejana, Elisabet ...
-
Felbor, Ute
-
visa färre...
- Om ämnet
-
- NATURVETENSKAP
-
NATURVETENSKAP
-
och Biologi
-
och Cellbiologi
- Artiklar i publikationen
-
Cellular and Mol ...
- Av lärosätet
-
Uppsala universitet