Single-cell analysis of the brain metastatic microenvironment in breast cancer

Identification: Evans, Katrina


Description

Single-cell analysis of the brain metastatic microenvironment in breast cancer
 
Katrina T. Evans1, Kerrigan Blake1, Quy Nguyen1, Devon Lawson1
University of California Irvine
 
Breast cancer brain metastasis affects 10-20% of patients, and there are no effective treatments. Activated infiltrating microglia and astrocytes are a major component of metastatic breast tumors in the brain, but it is not known whether these cells are involved in the promotion or rejection of breast cancer cells. To characterize the brain metastatic microenvironment, we used a FACS-based approach to capture pure and viable microglia and astrocytes from normal and metastatic mouse brains for single cell mRNA sequencing analysis. Using this approach, we have created a large single cell RNAseq data set containing microglia and astrocytes from normal and metastatic brains. Applying our analysis pipelines to this data revealed distinct pathways and markers associated with microglia and astrocytes in metastatic brains. Future work will aim to identify spatial locations and function of specific microglia and astrocyte sub-populations in the metastatic brain.  
 
Literature Cited: 1. Witzel, I., et al., Breast cancer brain metastases: biology and new clinical perspectives. Breast Cancer Res, 2016. 18(1). 2. Steeg, P.S., Targeting metastasis. Nat Rev Cancer, 2016. 16(4): p. 201-18  .3. Lorger, M. et al., Capturing changes in the brain microenvironment during initial steps of breast cancer brain metastasis. Am J Pathol, 2010. 176(6): p. 2958-71. 4. Spangenberg EE, Rice RA, Elmore MRP, Blurton-Jones M, West BL, Green KN. Brain, 2016, 169(4).  5. Liddelow, S. A. et al., Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 2017, 541, 481-487. 6. Bohlen, C. J. et al., Diverse Requirements for microglial Survival, Specification and Function Revealed by Defined- Medium Cultures. Neuron,  2017, 9, 759-773
 

Literature Cited: 1. Witzel, I., et al., Breast cancer brain metastases: biology and new clinical perspectives. Breast Cancer Res, 2016. 18(1). 2. Steeg, P.S., Targeting metastasis. Nat Rev Cancer, 2016. 16(4): p. 201-18  .3. Lorger, M. et al., Capturing changes in the brain microenvironment during initial steps of breast cancer brain metastasis. Am J Pathol, 2010. 176(6): p. 2958-71. 4. Spangenberg EE, Rice RA, Elmore MRP, Blurton-Jones M, West BL, Green KN. Brain, 2016, 169(4).  5. Liddelow, S. A. et al., Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 2017, 541, 481-487. 6. Bohlen, C. J. et al., Diverse Requirements for microglial Survival, Specification and Function Revealed by Defined- Medium Cultures. Neuron,  2017, 9, 759-773
 
 

Credits

Credits: None available.

You must be logged in and own this product in order to post comments.