Hypoxia-induced up-regulation of angiopoietin-2 in colorectal cancer.
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.
Gu
Jinyu
J
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Yamamoto
Hirofumi
H
Ogawa
Minoru
M
Ngan
Chew Yee
CY
Danno
Katsuki
K
Hemmi
Hideyuki
H
Kyo
Naganori
N
Takemasa
Ichiro
I
Ikeda
Masataka
M
Sekimoto
Mitsugu
M
Monden
Morito
M
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
D042702:Angiopoietin-2; D016895:Culture Media, Serum-Free; D051272:Glucose Transporter Type 1; D012333:RNA, Messenger