Hypoxia-induced up-regulation of angiopoietin-2 in colorectal cancer

Oncol Rep. 2006 Apr;15(4):779-83.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-2 / analysis
  • Angiopoietin-2 / genetics*
  • Cell Hypoxia / physiology*
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Culture Media, Serum-Free / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Glucose Transporter Type 1 / genetics
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Hypoxia / physiopathology*
  • Immunohistochemistry
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Angiopoietin-2
  • Culture Media, Serum-Free
  • Glucose Transporter Type 1
  • RNA, Messenger