Incipient melanoma brain metastases instigate astrogliosis and neuroinflammation

• Verfasst von: Schwartz, Hila [VerfasserIn]
• Verfasst von: Umansky, Viktor [VerfasserIn]
• Titel: Incipient melanoma brain metastases instigate astrogliosis and neuroinflammation
• Verf.angabe: Hila Schwartz, Eran Blacher, Malak Amer, Nir Livneh, Lilach Abramovitz, Anat Klein, Dikla Ben-Shushan, Shelly Soffer, Raquel Blazquez, Alonso Barrantes-Freer, Meike Müller, Karin Müller-Decker, Reuven Stein, Galia Tsarfaty, Ronit Satchi-Fainaro, Viktor Umansky, Tobias Pukrop, and Neta Erez
• E-Jahr: 2016
• Jahr: June 3, 2016
• Umfang: 14 S.
• Fussnoten: Gesehen am 14.08.2019
• Titel Quelle: Enthalten in: Cancer research
• Ort Quelle: Philadelphia, Pa. : AACR, 1916
• Jahr Quelle: 2016
• Band/Heft Quelle: 76(2016), 15, Seite 4359-4371
• ISSN Quelle: 1538-7445
• DOI: doi:10.1158/0008-5472.CAN-16-0485
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1671403843

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.