Hypoxia enhances CXCR4 expression by activating HIF-1 in oral squamous cell carcinoma.
Hypoxia promotes the invasive and metastatic potential of tumour cells. A recent study has shown that the activation of the chemokine receptor CXCR4 by lack of oxygen in breast cancer is HIF-1-dependent. We have previously demonstrated that CXCR4 signalling is involved in the establishment of lymph node metastasis in oral squamous cell carcinoma (OSCC). In this study, we investigated a correlation between CXCR4 and HIF-1alpha expression in OSCC. Immunohistochemistry showed that CXCR4 was expressed in 20 of 85 OSCC tissues, while HIF-1alpha was expressed in 51 of 85 samples. There was a significant correlation between the expression of CXCR4 and HIF-1alpha. In human OSCC cells, hypoxia markedly enhanced the expression of both HIF-1alpha and CXCR4. Furthermore, synthetic small interfering RNA specific for HIF-1alpha significantly suppressed the expression of this protein, and also attenuated the induction of CXCR4 expression under hypoxic conditions. These results indicated that HIF-1alpha regulated hypoxia-induced CXCR4 expression in OSCC.
Ishikawa
Tohru
T
Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan.
Nakashiro
Koh-ichi
K
Klosek
Sebastian K
SK
Goda
Hiroyuki
H
Hara
Shingo
S
Uchida
Daisuke
D
Hamakawa
Hiroyuki
H
D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C527276:CXCR4 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4