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Incipient Melanoma Brain Metastases Instigate Astrogliosis and Neuroinflammation
- Source :
- Cancer research. 76(15)
- Publication Year :
- 2016
-
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. Cancer Res; 76(15); 4359–71. ©2016 AACR.
- Subjects :
- 0301 basic medicine
Cancer Research
Pathology
medicine.medical_specialty
Skin Neoplasms
Inflammation
Neovascularization
03 medical and health sciences
Mice
0302 clinical medicine
medicine
Animals
Humans
Neoplasm Metastasis
Melanoma
Neuroinflammation
Neovascularization, Pathologic
business.industry
Brain Neoplasms
Cancer
medicine.disease
3. Good health
Astrogliosis
Disease Models, Animal
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Astrocytes
Damage response
medicine.symptom
business
Brain metastasis
Subjects
Details
- ISSN :
- 15387445
- Volume :
- 76
- Issue :
- 15
- Database :
- OpenAIRE
- Journal :
- Cancer research
- Accession number :
- edsair.doi.dedup.....b6940f9e20365f87aa616d2737935981