Blazquez, Raquel and Chuang, Han-Ning and Wenske, Britta and Trigueros, Laura and Wlochowitz, Darius and Liguori, Renato and Ferrazzi, Fulvia and Regen, Tommy and Proescholdt, Martin A. and Rohde, Veit and Riemenschneider, Markus J. and Stadelmann, Christine and Bleckmann, Annalen and Beissbarth, Tim and van Rossum, Denise and Hanisch, Uwe K. and Pukrop, Tobias (2022) Intralesional TLR4 agonist treatment strengthens the organ defense against colonizing cancer cells in the brain. ONCOGENE, 41 (46). pp. 5008-5019. ISSN 0950-9232, 1476-5594
Full text not available from this repository. (Request a copy)Abstract
Brain metastasis in breast cancer remains difficult to treat and its incidence is increasing. Therefore, the development of new therapies is of utmost clinical relevance. Recently, toll-like receptor (TLR) 4 was correlated with IL6 expression and poor prognosis in 1 215 breast cancer primaries. In contrast, we demonstrated that TLR4 stimulation reduces microglia-assisted breast cancer cell invasion. However, the expression, prognostic value, or therapeutic potential of TLR signaling in breast cancer brain metastasis have not been investigated. We thus tested the prognostic value of various TLRs in two brain-metastasis gene sets. Furthermore, we investigated different TLR agonists, as well as MyD88 and TRIF-deficient microenvironments in organotypic brain-slice ex vivo co-cultures and in vivo colonization experiments. These experiments underline the ambiguous roles of TLR4, its adapter MyD88, and the target nitric oxide (NO) during brain colonization. Moreover, analysis of the gene expression datasets of breast cancer brain metastasis patients revealed associations of TLR1 and IL6 with poor overall survival. Finally, our finding that a single LPS application at the onset of colonization shapes the later microglia/macrophage reaction at the macro-metastasis brain-parenchyma interface (MMPI) and reduces metastatic infiltration into the brain parenchyma may prove useful in immunotherapeutic considerations.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BREAST-CANCER; NITRIC-OXIDE; PROMOTES; RECEPTOR; METASTASIS; MICROENVIRONMENT; INTERFACE; TISSUE; GENE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Neurochirurgie Medicine > Abteilung für Neuropathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Feb 2024 10:31 |
| Last Modified: | 20 Feb 2024 10:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57597 |
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