Hosseini, Hedayatollah and Obradovic, Milan M. S. and Hoffmann, Martin and Harper, Kathryn L. and Sosa, Maria Soledad and Werner-Klein, Melanie and Nanduri, Lahiri Kanth and Werno, Christian and Ehrl, Carolin and Maneck, Matthias and Patwary, Nina and Haunschild, Gundula and Guzvic, Miodrag and Reimelt, Christian and Grauvogl, Michael and Eichner, Norbert and Weber, Florian and Hartkopf, Andreas D. and Taran, Florin-Andrei and Rucker, Sara Y. B. and Fehm, Tanja and Rack, Brigitte and Buchholz, Stefan and Spang, Rainer and Eister, Gunter M. and Aguirre-Ghiso, Julio A. and Klein, Christoph A. (2016) Early dissemination seeds metastasis in breast cancer. NATURE, 540 (7634). 552-+. ISSN 0028-0836, 1476-4687
Full text not available from this repository. (Request a copy)Abstract
Accumulating data suggest that metastatic dissemination often occurs early during tumour formation, but the mechanisms of early metastatic spread have not yet been addressed. Here, by studying metastasis in a HER2-driven mouse breast cancer model, we show that progesterone-induced signalling triggers migration of cancer cells from early lesions shortly after HER2 activation, but promotes proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by increased HER2 expression and tumour-cell density involving microRNA-mediated progesterone receptor downregulation, and was reversible. Cells from early, low-density lesions displayed more stemness features, migrated more and founded more metastases than cells from dense, advanced tumours. Notably, we found that at least 80% of metastases were derived from early disseminated cancer cells. Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DISSEMINATED TUMOR-CELLS; COMPARATIVE GENOMIC HYBRIDIZATION; MAMMARY-GLAND DEVELOPMENT; MINIMAL RESIDUAL CANCER; CDNA MICROARRAY DATA; CARCINOMA IN-SITU; ARRAY CGH DATA; BONE-MARROW; MOUSE MODEL; STEM-CELLS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Pathologie Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Apr 2019 11:15 |
| Last Modified: | 11 Apr 2019 11:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3768 |
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