Obesity is a known risk factor for breast cancer. Since obesity rates are constantly rising worldwide, understanding the molecular details of the interaction between adipose tissue and breast tumors becomes an urgent task. To investigate potential molecular changes in breast cancer cells induced by co-existing adipocytes, we used a co-culture system of different breast cancer cell lines (MCF-7 and T47D: ER+/PR+/HER2- and MDA-MB-231: ER-/PR-/HER2-) and murine 3T3-L1 adipocytes. Here, we report that co-culture with adipocytes revealed distinct changes in global gene expression pattern in the different breast cancer cell lines. Our microarray data revealed that in both ER+ cell lines, top upregulated genes showed significant enrichment for hormone receptor target genes. In triple-negative MDA-MB-231 cells, co-culture with adipocytes led to the induction of pro-inflammatory genes, mainly involving genes of the Nf-κB signaling pathway. Moreover, co-cultured MDA-MB-231 cells showed increased secretion of the pro-inflammatory interleukins IL-6 and IL-8. Using a specific NF-κB inhibitor, these effects were significantly decreased. Finally, migratory capacities were significantly increased in triple-negative breast cancer cells upon co-culture with adipocytes, indicating an enhanced aggressive cell phenotype. Together, our studies illustrate that factors secreted by adipocytes have a significant impact on the molecular biology of breast cancer cells.:1. Einleitung ......................................................................................................... 4
1.1 Übergewicht und Adipositas – die Volkskrankheit des 21. Jahrhunderts ........ 4
1.2 Fettgewebe – Fett ist nicht gleich Fett ........................................................... 5
1.3 Fehlfunktionen des Fettgewebes bei Adipositas ............................................ 6
1.4 Der Zusammenhang zwischen Adipositas und Krebs ..................................... 7
1.4.1 Adipositas und die Tumormikroumgebung .................................................. 7
1.4.2 Adipositas-induzierte Inflammation und Krebs ............................................. 9
1.4.3 Die Insulin-IGF1-Achse................................................................................11
1.4.4 Östrogen-Synthese in adipösem Fettgewebe ............................................12
1.4.5 Tumorzellmetabolismus ..............................................................................12
1.5 Ziele der Arbeit ............................................................................................. 14
2 Publikation ...................................................................................................... 15
3 Zusammenfassung der Arbeit ......................................................................... 29
4 Literaturverzeichnis.......................................................................................... 34
5 Anlagen ........................................................................................................... 43
5.1 Supplemental Material .................................................................................. 43
5.1.1 Supplemental Figures ................................................................................45
5.1.2 Supplemental Tables ..................................................................................51
5.2 Erklärung über den wissenschaftlichen Beitrag des Promovenden zur Publikation ......................................................................................................... 66
5.3 Verzeichnis der verwendeten Abkürzungen und Symbole ............................ 67
5.4 Erklärung über die eigenständige Abfassung der Arbeit .............................. 69
5.5 Lebenslauf ................................................................................................... 70
5.6 Publikationsverzeichnis ................................................................................ 72
5.7 Vorträge und Posterpräsentationen mit publizierten Abstracts ..................... 73
5.8 Danksagung ................................................................................................. 74
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:33643 |
| Date | 26 March 2019 |
| Creators | Nickel, Annina |
| Contributors | Universität Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | German |
| Detected Language | English |
| Type | info:eu-repo/semantics/acceptedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 10.1038/s41598-018-27210-w |
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