The perivascular niche regulates breast tumour dormancy Journal Article
| Authors: | Ghajar, C. M.; Peinado, H.; Mori, H.; Matei, I. R.; Evason, K. J.; Brazier, H.; Almeida, D.; Koller, A.; Hajjar, K. A.; Stainier, D. Y. R.; Chen, E. I.; Lyden, D.; Bissell, M. J. |
| Article Title: | The perivascular niche regulates breast tumour dormancy |
| Abstract: | In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumour cells (DTCs) are kept dormant, and what wakes them up, are fundamental problems in tumour biology. To address these questions, we used metastasis assays in mice and showed that dormant DTCs reside on microvasculature of lung, bone marrow and brain. We then engineered organotypic microvascular niches to determine whether endothelial cells directly influence breast cancer cell (BCC) growth. These models demonstrated that endothelial-derived thrombospondin-1 induces sustained BCC quiescence. This suppressive cue was lost in sprouting neovasculature; time-lapse analysis showed that sprouting vessels not only permit, but accelerate BCC outgrowth. We confirmed this surprising result in dormancy models and in zebrafish, and identified active TGF-β1 and periostin as tumour-promoting factors derived from endothelial tip cells. Our work reveals that stable microvasculature constitutes a dormant niche, whereas sprouting neovasculature sparks micrometastatic outgrowth. © 2013 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | controlled study; cancer growth; nonhuman; brain neoplasms; mouse; animals; mice; animal tissue; mus; breast cancer; transforming growth factor beta; lung neoplasms; animal experiment; animal model; tumor cells, cultured; breast neoplasms; neovascularization, pathologic; endothelium cell; lung metastasis; fluorescent antibody technique; vascular endothelium; endothelium, vascular; neoplasm, residual; cancer cell; brain metastasis; transforming growth factor beta1; cell adhesion molecules; thrombospondin 1; microvasculature; tumor vascularization; stem cell niche; zebrafish; danio rerio; bone marrow neoplasms; tumor microenvironment; bone marrow metastasis; tumor dormancy; oncological parameters; transcription factor runx2; pericytes; microvascular niche |
| Journal Title: | Nature Cell Biology |
| Volume: | 15 |
| Issue: | 7 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2013-07-01 |
| Start Page: | 807 |
| End Page: | 817 |
| Language: | English |
| DOI: | 10.1038/ncb2767 |
| PROVIDER: | scopus |
| PUBMED: | 23728425 |
| PMCID: | PMC3826912 |
| DOI/URL: | |
| Notes: | --- - Cited By (since 1996):1 - "Export Date: 1 August 2013" - "CODEN: NCBIF" - "Source: Scopus" |
