Details

Autor(en) / Beteiligte

• Koike, Tetsufumi
• Kimura, Naoko
• Miyazaki, Keiko
• Yabuta, Tomonori
• Kumamoto, Kensuke
• Takenoshita, Seiichi
• Chen, Jian
• Kobayashi, Masanobu
• Hosokawa, Masuo
• Taniguchi, Akiyoshi
• Kojima, Tetsuhito
• Ishida, Nobuhiro
• Kawakita, Masao
• Yamamoto, Harumi
• Takematsu, Hiromu
• Suzuki, Akemi
• Kozutsumi, Yasunori
• Kanangi, Reiji
• Fischer, Edmond H.

Titel

Hypoxia Induces Adhesion Molecules on Cancer Cells: A Missing Link between Warburg Effect and Induction of Selectin-Ligand Carbohydrates

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2004-05, Vol.101 (21), p.8132-8137

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• Cancer cells undergo distinct metabolic changes to cope with their hypoxic environment. These changes are achieved at least partly by the action of transcriptional factors called hypoxia-inducible factors (HIFs). We investigated gene expression in cultured human colon cancer cells induced by hypoxic conditions with special reference to cell-adhesion molecules and carbohydrate determinants having cell-adhesive activity by using DNA-microarray and RT-PCR techniques. Hypoxic culture of colon cancer cells induced a marked increase in expression of selectin ligands, the sialyl Lewis x and sialyl Lewis a determinants at the cell surface, which led to a definite increase in cancer cell adhesion to endothelial E-selectin. The transcription of genes for fucosyltransferase VII (FUT7), sialyl-transferase ST3Gal-I (ST3O), and UDP-galactose transporter-1 (UGT1), which are all known to be involved in the synthesis of the carbohydrate ligands for E-selectin, was significantly induced in cancer cells by hypoxic culture. In addition, a remarkable induction was detected in the genes for syndecan-4 (SDC4) and α5-integrin (ITGA5), the cell-adhesion molecules involved in the enhanced adhesion of cancer cells to fibronectin. The transcriptional induction by hypoxia was reproduced in the luciferase-reporter assays for these genes, which were significantly suppressed by the cotransfection of a dominant-negative form of HIF. These results indicate that the metabolic shifts of cancer cells partly mediated by HIFs significantly enhance their adhesion to vascular endothelial cells, through both selectin- and integrin-mediated pathways, and suggest that this enhancement further facilitates hematogenous metastasis of cancers and tumor angiogenesis.