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The role of histamine in opening blood-tumor barrier.
- Source :
-
Oncotarget [Oncotarget] 2016 May 24; Vol. 7 (21), pp. 31299-310. - Publication Year :
- 2016
-
Abstract
- Blood-tumor barrier (BTB) reduce the permeability for drugs into tumor tissues. We found that histamine might serve as an essential regulator of BTB function. Further, we aim to determine the role of H2 receptor expression in BTB permeability, and elucidate the underlying mechanisms thereof. Transmission electron microscopy showed that histamine disrupted the integrity of tight junctions (TJ) and increased the number of pinosomes in the cytoplasm. Horseradish peroxidase (HRP) and trans-endothelial resistance detection (TEER) assays revealed that histamine could open BTB and this action was inhibited by cimetidine. Western blot and immunofluorescence assays showed that histamine decreased the expression of tight junction proteins zonula occluden-1(ZO-1), occludin, and claudin-5. Further, quantitative RT-PCR assay showed that the expression of H2 receptor could represent and predicted histamine-induced BTB permeability. In conclusion, histamine opened BTB by down-regulating the TJ-associated proteins. The levels of H2 receptor expression was correlated with the histamine-induced BTB permeability.<br />Competing Interests: The authors have no potential conflicts of interest.
- Subjects :
- Animals
Blood-Brain Barrier metabolism
Blood-Brain Barrier physiopathology
Blotting, Western
Brain Neoplasms blood supply
Brain Neoplasms metabolism
Brain Neoplasms pathology
Cell Line, Tumor
Cells, Cultured
Coculture Techniques
Endothelial Cells cytology
Endothelial Cells metabolism
Glioma blood supply
Glioma metabolism
Glioma pathology
Microscopy, Electron, Transmission
Permeability drug effects
Rats, Sprague-Dawley
Receptors, Histamine H2 metabolism
Tight Junctions metabolism
Tight Junctions ultrastructure
Zonula Occludens-1 Protein metabolism
Blood-Brain Barrier drug effects
Histamine pharmacology
Tight Junctions drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27121317
- Full Text :
- https://doi.org/10.18632/oncotarget.8896