title: Tumour endothelial cells acquire drug resistance in a tumour microenvironment.
abstract: Tumour growth is dependent on angiogenesis, and tumour blood vessels are recognized as an important target for cancer therapy. Tumour endothelial cells (TECs) are the main targets of anti-angiogenic therapy. Unlike the traditionally held view, some TECs may be genetically abnormal and might acquire drug resistance. Therefore, we investigated the drug resistance of TECs and the mechanism by which it is acquired. TECs show resistance to paclitaxel through greater mRNA expression of multidrug resistance 1, which encodes P-glycoprotein, as compared with normal endothelial cells. We found that high levels of vascular endothelial growth factor in tumour-conditioned medium may be responsible for upregulated P-glycoprotein expression. This is a novel mechanism for the acquisition of drug resistance by TECs in a tumour microenvironment. This review focuses on the possibility that TECs can acquire drug resistance.
authors.affiliation: Department of Vascular Biology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan. khida@den.hokudai.ac.jp
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hida
authors.forename: Kosuke
authors.initials: K
authors.lastname: Akiyama
authors.forename: Noritaka
authors.initials: N
authors.lastname: Ohga
authors.forename: Nako
authors.initials: N
authors.lastname: Maishi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hida
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D059016:Tumor Microenvironment / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D042461:Vascular Endothelial Growth Factor A