Genes that mediate breast cancer metastasis to the brain
By Paula D. Bos, X. Zhang, C. Nadal, Weiping Shu, R. Gomis, D. Nguyen, Andy J. Minn, M. J. van de Vijver, W. Gerald, John A. Foekens and 1 more. Nature, 2009
1,825 citations recorded by the source corpus.
The molecular basis for breast cancer metastasis to the brain is largely unknown. Brain relapse typically occurs years after the removal of a breast tumour, suggesting that disseminated cancer cells must acquire specialized functions to take over this organ. Here we show that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood–brain barrier crossing and brain colonization. We isolated cells that preferentially infiltrate the brain from patients with advanced disease. Gene expression analysis of these cells and of clinical samples, coupled with functional analysis, identified the cyclooxygenase COX2 (also known as PTGS2), the epidermal growth factor receptor (EGFR) ligand HBEGF, and the α2,6-sialyltransferase ST6GALNAC5 as mediators of cancer cell passage through the blood–brain barrier. EGFR ligands and COX2 were previously linked to breast cancer infiltration of the lungs, but not the bones or liver, suggesting a sharing of these mediators in cerebral and pulmonary metastases. In contrast, ST6GALNAC5 specifically mediates brain metastasis. Normally restricted to the brain, the expression of ST6GALNAC5 in breast cancer cells enhances their adhesion to brain endothelial cells and their passage through the blood–brain barrier. This co-option of a brain sialyltransferase highlights the role of cell-surface glycosylation in organ-specific metastatic interactions.
Subfields: Oncology, Psychiatry and Mental health, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/1808cdb45986ed94966315bf25bc850a64df2e72
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Citations in the corpus
- Tumor Metastasis: Molecular Insights and Evolving Paradigms (2011, neutral): “More recently, a number of genes whose expression facilitates the metastatic colonization of breast cancer cells specifically to either bone (Kang et al., 2003), lung (Minn et al., 2005), brain (Bos et al., 2009), or liver (Tabariès et al., 2011) have been identified.”
- Heterogeneous Blood-Tumor Barrier Permeability Determines Drug Efficacy in Experimental Brain Metastases of Breast Cancer (2010, positive): “Herein, we explore these questions using two recently established experimental models of brain metastasis that arise from the systemic circulation (39, 40).”
- The microenvironmental landscape of brain tumors (2017, background): “In other studies, additional factors have been identified as potential site-specificmediators of BBB transmigration, including PTGS2, HB-EGF, ST6GALNAC5 (Bos et al., 2009), PLEKHA5 (Jilaveanu et al., 2015), and the serum factor PLGF (Li et al., 2013).”
- Triple Negative Breast Cancer Cell Lines: One Tool in the Search for Better Treatment of Triple Negative Breast Cancer (2010, background): “For example, global expression analysis identified high expression of cyclooxygenase 2, heparin-binding epidermal growth factor, and the α2,6 sialotransferase ST6GALNAC5 in the subclones of MDA-MB-231 that preferentially metastasize to the brain [89].”
- An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients (2010, neutral): “8 NA NA NA 204 [23] GSE16391 GPL570 55(100%) 33(60%) 55(100%) 3.”