TMIC-34. IN VITRO STUDY OF ROLE OF ASTROCYTIC S1P3 IN REGULATING BLOOD-BRAIN/TUMOR BARRIER PERMEABILITY

Incidence of breast cancer brain metastasis is increasing. Prognosis of patients with brain metastases is extremely poor. One of the major impediments in treating brain metastases is the presence of a blood-brain/tumor barrier that limits the permeability of chemotherapeutic drugs into the brain par...

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Published in:Neuro-oncology (Charlottesville, Va.) Va.), 2017-11, Vol.19 (suppl_6), p.vi250-vi250
Main Authors: Paranjape, Anurag N, Gril, Brunilde, Woditschka, Stephan, Hanson, Jeffrey, Wu, Xiaolin, Pauly, Gary T, Schneider, Joel P, Steeg, Patricia
Format: Article
Language:English
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Summary:Incidence of breast cancer brain metastasis is increasing. Prognosis of patients with brain metastases is extremely poor. One of the major impediments in treating brain metastases is the presence of a blood-brain/tumor barrier that limits the permeability of chemotherapeutic drugs into the brain parenchyma. Blood-tumor barrier (BTB) has been shown to be heterogenous, and only at highly permeable lesions do drugs reach the tumor cells. To explore the molecular differences between highly and poorly permeable BTBs, gene profiling was done on laser microdissected brain tissues from mice bearing breast cancer brain metastases. Sphingosine-1-phosphate receptor 3 (S1P3) was overexpressed in astrocytes at highly permeable lesions. To explore the functional role of S1P3 in BTB permeability we established an in vitro blood brain/tumor model. Inhibition of S1P3 using a specific chemical inhibitor TY-52156 (2µM) significantly increased barrier integrity as shown by increase in transendothelial electrical resistance (TEER) in BBB (1.3 folds, p
ISSN:1522-8517
1523-5866
DOI:10.1093/neuonc/nox168.1022