title: Heterogeneity of tumor endothelial cells: comparison between tumor endothelial cells isolated from high- and low-metastatic tumors.
abstract: An important concept in tumor angiogenesis is that tumor endothelial cells (TECs) are genetically normal and homogeneous. However, we previously reported that TECs differ from normal ECs. Whether the characteristics of TECs derived from different tumors differ remains unknown. To elucidate this, in this study, we isolated two types of TECs from high-metastatic (HM) and low-metastatic (LM) tumors and compared their characteristics. HM tumor-derived TECs (HM-TECs) showed higher proliferative activity and invasive activity than LM tumor-derived TECs (LM-TECs). Moreover, the mRNA expression levels of pro-angiogenic genes, such as vascular endothelial growth factor (VEGF) receptors 1 and 2, VEGF, and hypoxia-inducible factor-1α, were higher in HM-TECs than in LM-TECs. The tumor blood vessels themselves and the surrounding area in HM tumors were exposed to hypoxia. Furthermore, HM-TECs showed higher mRNA expression levels of the stemness-related gene stem cell antigen and the mesenchymal marker CD90 compared with LM-TECs. HM-TECs were spheroid, with a smoother surface and higher circularity in the stem cell spheroid assay. HM-TECs differentiated into osteogenic cells, expressing activated alkaline phosphatase in an osteogenic medium at a higher rate than either LM-TECs or normal ECs. Furthermore, HM-TECs contained more aneuploid cells than LM-TECs. These results indicate that TECs from HM tumors have a more pro-angiogenic phenotype than those from LM tumors.
authors.affiliation: Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Hokkaido, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Ohga
authors.affiliation: Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Hokkaido, Japan; Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Hokkaido, Japan.
authors.forename: Nako
authors.initials: N
authors.lastname: Maishi
authors.affiliation: Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Hokkaido, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Akiyama
authors.affiliation: Department of Surgical Oncology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hida
authors.affiliation: Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Hokkaido, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kawamoto
authors.affiliation: Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Hokkaido, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sadamoto
authors.affiliation: Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Hokkaido, Japan; Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Osawa
authors.affiliation: Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Hokkaido, Japan; Department of Surgical Oncology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Hokkaido, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Kondoh
authors.affiliation: Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Hokkaido, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ohmura
authors.affiliation: Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shinohara
authors.affiliation: Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nonomura
authors.affiliation: Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Hokkaido, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Shindoh
authors.affiliation: Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Hokkaido, Japan. Electronic address: khida@den.hokudai.ac.jp.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hida
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000782:Aneuploidy; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D020286:Pericytes / Q000473:pathology; D010641:Phenotype; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1