Claudin-10 in the blood brain barrier function of cerebral endothelial cells and transendothelial invasion of breast cancer cells

Zhuang, Xinguo, Ji, Wenxiao, Fang, Ziqian, Yang, Yiming, Ruge, Fiona, Dou, Q. Ping, Li, Xun, Xu, Bing, Jiang, Wen G. ORCID: https://orcid.org/0000-0002-3283-1111 and Martin, Tracey A. ORCID: https://orcid.org/0000-0003-2690-4908 2023. Claudin-10 in the blood brain barrier function of cerebral endothelial cells and transendothelial invasion of breast cancer cells. Anticancer Research 43 (9) , pp. 3923-3934. 10.21873/anticanres.16580

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Abstract

Background/Aim: Claudin-10 (CLDN10) is a membrane integral protein. It is one of the widely expressed tight junctional claudins with functions not well defined. In the present study, the expression profile and its role in cerebral endothelial cells and in the interaction between breast cancer and endothelial cells were investigated. Materials and Methods: CLDN10 expression was examined in a wide range of cell types. Brain endothelial cell models with or without CLDN10 expression were generated using the hCMEC/D3 cell line and used to test the barrier and permeability functions. Transendothelial drug delivery and invasion were also evaluated. Results: hCMEC/D3 cells express high levels of CLDN10, compared with peripheral endothelial cells, mesothelial cells, fibroblasts, and breast cancer cells, which were either negative or expressed low levels of CLDN10. Knockdown of CLDN10 in hCMEC/D3 cells resulted in impaired tight junctions as seen by reduced transendothelial electric resistance and paracellular permeability. It also accelerated invasion of breast cancer cells through the endothelial cell layer. CLDN10 knockdown in hCMEC/D3 cells led to an increase in transendothelial chemodrug delivery. Furthermore, the SRC kinase inhibitor (AZM475271) was able to decrease the impedance and increase the paracellular permeability in cerebral endothelial cells. Conclusion: Cerebral endothelial cells express high levels of CLDN10, a protein regulating barrier function and thereby drug permeability and cancer invasiveness in brain endothelial cells, suggesting that it is a novel therapeutic target for the treatment of brain metastasis-related diseases.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	International Institute of Anticancer Research
ISSN:	0250-7005
Funders:	Xiamen Medical and Health Guidance Project (No.3502Z20224ZD1014), the Natural Scientific Foundation of Xiamen (No.3502Z20227340), the Fujian Natural Science Foundation of China (No. 2022J011372) and the National Natural Science Foundation of China (No. 81871305); Dr. Xinguo Zhuang is supported by the Cardiff University-Xiamen University Strategic Partnership Fund
Date of First Compliant Deposit:	4 August 2023
Date of Acceptance:	26 July 2023
Last Modified:	06 Jan 2024 04:30
URI:	https://orca.cardiff.ac.uk/id/eprint/161459

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