Clinical & Experimental Metastasis

, Volume 25, Issue 7, pp 799–810

Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization

Authors

    • Women’s Cancers Section, Laboratory of Molecular PharmacologyNational Cancer Institute
  • Diane Palmieri
    • Women’s Cancers Section, Laboratory of Molecular PharmacologyNational Cancer Institute
  • Emily Hua
    • Women’s Cancers Section, Laboratory of Molecular PharmacologyNational Cancer Institute
  • Elizabeth Hargrave
    • Women’s Cancers Section, Laboratory of Molecular PharmacologyNational Cancer Institute
  • Jeanne M. Herring
    • Laboratory Animal Sciences Program, Science Applications International Corporation-FrederickNational Cancer Institute NIH
  • Yongzhen Qian
    • Laboratory Animal Sciences Program, Science Applications International Corporation-FrederickNational Cancer Institute NIH
  • Eleazar Vega-Valle
    • Laboratory Animal Sciences Program, Science Applications International Corporation-FrederickNational Cancer Institute NIH
  • Robert J. Weil
    • Department of Neurosurgery and Neurological InstituteBrain Tumor & Neuro-Oncology Center, Cleveland Clinic
  • Andreas M. Stark
    • Department of NeurosurgerySchleswig-Holstein University Medical Center
  • Alexander O. Vortmeyer
    • Surgical Neurology BranchNational Institute of Neurological Disorders and Stroke NIH
  • Patricia S. Steeg
    • Women’s Cancers Section, Laboratory of Molecular PharmacologyNational Cancer Institute
Research Paper

DOI: 10.1007/s10585-008-9193-z

Cite this article as:
Fitzgerald, D.P., Palmieri, D., Hua, E. et al. Clin Exp Metastasis (2008) 25: 799. doi:10.1007/s10585-008-9193-z

Abstract

Interactions between tumor cells and the microenvironment are crucial to tumor formation and metastasis. The central nervous system serves as a “sanctuary” site for metastasis, resulting in poor prognosis in diagnosed patients. The incidence of brain metastasis is increasing; however, little is known about interactions between the brain and metastatic cells. Brain pathology was examined in an experimental model system of brain metastasis, using a subline of MDA-MB-231 human breast cancer cells. The results were compared with an analysis of sixteen resected human brain metastases of breast cancer. Experimental metastases formed preferentially in specific brain regions, with a distribution similar to clinical cases. In both the 231-BR model, and in human specimens, Ki67 expression indicated that metastases were highly proliferative (~50%). Little apoptosis was observed in either set of tumors. In the model system, metastases elicited a brain inflammatory response, with extensive reactive gliosis surrounding metastases. Similarly, large numbers of glial cells were found within the inner tumor mass of human brain metastases. In vitro co-cultures demonstrated that glia induced a ~5-fold increase in metastatic cell proliferation (P < 0.001), suggesting that brain tissue secretes factors conducive to tumor cell growth. Molecules used to signal between tumor cells and the surrounding glia could provide a new avenue of therapeutic targets for brain metastases.

Keywords

Brain metastasis Brain pathology Breast cancer Neuroinflammation Reactive glia Xenograft

Abbreviations

DAPI 4′6

Diamidino-2-phenylindole

EGFP

Enhanced Green Fluorescent Protein

GFAP

Glial Fibrillary Acidic Protein

H&E

Hematoxylin and eosin

Copyright information

© Springer Science+Business Media B.V. 2008