Schwartz, Hila and Blacher, Eran and Amer, Malak and Livneh, Nir and Abramovitz, Lilach and Klein, Anat and Ben-Shushan, Dikla and Soffer, Shelly and Blazquez, Raquel and Barrantes-Freer, Alonso and Mueller, Meike and Mueller-Decker, Karin and Stein, Reuven and Tsarfaty, Galia and Satchi-Fainaro, Ronit and Umansky, Viktor and Pukrop, Tobias and Erez, Neta (2016) Incipient Melanoma Brain Metastases Instigate Astrogliosis and Neuroinflammation. CANCER RESEARCH, 76 (15). pp. 4359-4371. ISSN 0008-5472, 1538-7445
Full text not available from this repository. (Request a copy)Abstract
Malignant melanoma is the deadliest of skin cancers. Melanoma frequently metastasizes to the brain, resulting in dismal survival. Nevertheless, mechanisms that govern early metastatic growth and the interactions of disseminated metastatic cells with the brain microenvironment are largely unknown. To study the hallmarks of brain metastatic niche formation, we established a transplantable model of spontaneous melanoma brain metastasis in immunocompetent mice and developed molecular tools for quantitative detection of brain micrometastases. Here we demonstrate that micrometastases are associated with instigation of astrogliosis, neuroinflammation, and hyperpermeability of the blood-brain barrier. Furthermore, we show a functional role for astrocytes in facilitating initial growth of melanoma cells. Our findings suggest that astrogliosis, physiologically instigated as a brain tissue damage response, is hijacked by tumor cells to support metastatic growth. Studying spontaneous melanoma brain metastasis in a clinically relevant setting is the key to developing therapeutic approaches that may prevent brain metastatic relapse. (C) 2016 AACR.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RET TRANSGENIC MICE; MALIGNANT-MELANOMA; MOUSE MODEL; NUDE-MICE; T-CELLS; ASTROCYTES; EXPRESSION; INFLAMMATION; PERMEABILITY; CHEMOTHERAPY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Mar 2019 13:45 |
| Last Modified: | 28 Mar 2019 13:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3545 |
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