title: Hypoxia-induced up-regulation of angiopoietin-2 in colorectal cancer.
abstract: Angiogenesis is a compensatory mechanism that enables malignant tumors to survive in an oxygen-deficient environment. To test our hypothesis that hypoxia stimulates the production of angiopoietin-2 (Ang-2) in colorectal cancer (CRC), we investigated the expression of Ang-2 in three cultured CRC cell lines, and in specimens from 11 CRC metastatic liver tumors. Hypoxia-induced Ang-2 mRNA expression was clearly evident in HCT116 cells that did not express Ang-2 under normoxic conditions. Ang-2 mRNA was detected only after 48 h in hypoxic serum-deprived cultures in a LoVo cell line, and under both normoxic and hypoxic conditions without any noticeable difference in the HT29 cells. There was a stepwise increase in Ang-2 expression from the periphery to the central part of the liver metastatic foci, whereas an inverse result was noted in tumor blood vessels, with a gradual decrease in CD31-positive ECs from the edge to the central region of the metastatic lesion. An expression pattern similar to Ang-2 was found in glucose transporter 1 (Glut-1), a known hypoxia-induced factor. These findings suggest that hypoxia plays an important role in inducing the expression of Ang-2 in CRC.
authors.affiliation: Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Gu
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Ogawa
authors.forename: Chew Yee
authors.initials: CY
authors.lastname: Ngan
authors.forename: Katsuki
authors.initials: K
authors.lastname: Danno
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hemmi
authors.forename: Naganori
authors.initials: N
authors.lastname: Kyo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.forename: Masataka
authors.initials: M
authors.lastname: Ikeda
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Sekimoto
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D042702:Angiopoietin-2 / Q000032:analysis / Q000235:genetics*; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D051272:Glucose Transporter Type 1 / Q000235:genetics; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D042702:Angiopoietin-2; D016895:Culture Media, Serum-Free; D051272:Glucose Transporter Type 1; D012333:RNA, Messenger