The role of histamine in opening blood-tumor barrier.
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.
Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, 310022, P.R. China.|Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, 310022, P.R. China.
Zeng
Z
Wang
Department of Pharmacy, Integrated Chinese and Western Medicine Hospital of Zhejiang Province, Hangzhou, 310003, P.R. China.
Xin-Jun
XJ
Cai
Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, 310022, P.R. China.|Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, P.R. China.
Jing
J
Qin
Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, 310022, P.R. China.|Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, P.R. China.
Fa-Jun
FJ
Xie
Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, 310022, P.R. China.|Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, P.R. China.
Na
N
Han
Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, 310022, P.R. China.|Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, P.R. China.
Hong-Yang
HY
Lu
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005910:Glioma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006632:Histamine / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D010539:Permeability / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D011970:Receptors, Histamine H2 / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
D011970:Receptors, Histamine H2; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D006632:Histamine
H2 receptor; blood-tumor barrier; histamine; tight junctions-associated proteins