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Endothelial cell clonal expansion in the development of cerebral cavernous malformations

Malinverno, Matteo (author)
FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, I-20139 Milan, Italy
Maderna, Claudio (author)
FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, I-20139 Milan, Italy
Abu Taha, Abdallah (author)
Uppsala universitet,Vaskulärbiologi
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Corada, Monica (author)
FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, I-20139 Milan, Italy
Orsenigo, Fabrizio (author)
FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, I-20139 Milan, Italy
Valentino, Mariaelena (author)
FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, I-20139 Milan, Italy
Pisati, Federica (author)
FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, I-20139 Milan, Italy;Cogentech Scarl, Histopathol Unit, I-20139 Milan, Italy
Fusco, Carmela (author)
Fdn IRCCS Casa Sollievo Sofferenza, Div Med Genet, I-71013 Foggia, Italy
Graziano, Paolo (author)
Fdn IRCCS Casa Sollievo Sofferenza, Pathol Unit, I-71013 Foggia, Italy
Giannotta, Monica (author)
FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, I-20139 Milan, Italy
Yu, Qing Cissy (author)
Chinese Acad Sci, State Key Lab Cell Biol, CAS Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China
Zeng, Yi Arial (author)
Chinese Acad Sci, State Key Lab Cell Biol, CAS Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China
Lampugnani, Maria Grazia (author)
FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, I-20139 Milan, Italy;Mario Negri Inst Pharmacol Res, I-20156 Milan, Italy
Magnusson, Peetra U. (author)
Uppsala universitet,Vaskulärbiologi
Dejana, Elisabetta (author)
Uppsala universitet,Vaskulärbiologi,FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, I-20139 Milan, Italy;Univ Milan, Sch Med, Dept Oncol & Haematooncol, I-20122 Milan, Italy
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 (creator_code:org_t)
2019-06-24
2019
English.
In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Cerebral cavernous malformation (CCM) is a neurovascular familial or sporadic disease that is characterised by capillary-venous cavernomas, and is due to loss-of-function mutations to any one of three CCM genes. Familial CCM follows a two-hit mechanism similar to that of tumour suppressor genes, while in sporadic cavernomas only a small fraction of endothelial cells shows mutated CCM genes. We reported that in mouse models and in human patients, endothelial cells lining the lesions have different features from the surrounding endothelium, as they express mesenchymal/stem-cell markers. Here we show that cavernomas originate from clonal expansion of few Ccm3-null endothelial cells that express mesenchymal/stem-cell markers. These cells then attract surrounding wild-type endothelial cells, inducing them to express mesenchymal/stem-cell markers and to contribute to cavernoma growth. These characteristics of Ccm3-null cells are reminiscent of the tumour-initiating cells that are responsible for tumour growth. Our data support the concept that CCM has benign tumour characteristics.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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