Hypoxia modulates CCR7 expression in head and neck cancers

被引:13
作者
Basheer, Haneen A. [1 ,2 ]
Pakanavicius, Edvinas [3 ]
Cooper, Patricia A. [1 ]
Shnyder, Steven D. [1 ]
Martin, Lisette [4 ]
Hunter, Keith D. [4 ]
Vinader, Victoria [1 ]
Afarinkia, Kamyar [1 ]
机构
[1] Univ Bradford, Inst Canc Therapeut, Bradford BD7 1DP, W Yorkshire, England
[2] Zarqa Univ, Fac Pharm, POB 132222, Zarqa 13132, Jordan
[3] UCL, Div Biosci, London WC1E 6BT, England
[4] Univ Sheffield, Sch Clin Dent, Sheffield S10 2TA, S Yorkshire, England
关键词
CCR7; Head and neck cancer; Hypoxia; HIF-1; alpha; Tumour grade; Tumour stage; SQUAMOUS-CELL CARCINOMA; CHEMOKINE RECEPTOR CCR7; LYMPH-NODE METASTASIS; TUMOR MICROENVIRONMENT; PROTEIN EXPRESSION; MIGRATION; IMPACT; HIF-1; RADIOTHERAPY; INVOLVEMENT;
D O I
10.1016/j.oraloncology.2018.03.014
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Background: The chemokine receptor CCR7 is expressed on lymphocytes and dendritic cells and is responsible for trafficking of these cells in and out of secondary lymphoid organs. It has recently been shown that CCR7 expression is elevated in a number of cancers, including head and neck cancers, and that its expression correlates to lymph node (LN) metastasis. However, little is known about the factors that can induce CCR7 expression in head and neck cancers. Method: We compared the protein expression and functional responses of CCR7 under normoxia and hypoxia in head and neck cancer cell lines OSC-19, FaDu, SCC-4, A-253 and Detroit-562 cultured as monolayers, spheroids, and grown in vivo as xenografts in balb/c mice. In addition, we analysed the correlation between hypoxia marker HIF-1 alpha and CCR7 expression in a tissue microarray comprising 80 clinical samples with various stages and grades of malignant tumour and normal tissue. Results: Under hypoxia, the expression of CCR7 is elevated in both in vitro and in vivo models. Furthermore, in malignant tissue, a correlation is observed between hypoxia marker HIF-1 alpha and CCR7 across all clinical stages. This correlation is also strong in early histological grade of tumours. Conclusion: Hypoxia plays a role in the regulation of the expression of CCR7 and it may contribute to the development of a metastatic phenotype in head and neck cancers through this axis.
引用
收藏
页码:64 / 73
页数:10
相关论文
共 60 条
[1]
Oxygen-independent Regulation of HIF-1: Novel Involvement of PI3K/AKT/mTOR Pathway in Cancer [J].
Agani, Faton ;
Jiang, Bing-Hua .
CURRENT CANCER DRUG TARGETS, 2013, 13 (03) :245-251
[2]
Ahmed M, 2017, SCI REP, P7
[3]
Targeting hypoxia to overcome radiation resistance in head & neck cancers: real challenge or clinical fairytale? [J].
Baumann, Rene ;
Depping, Reinhard ;
Delaperriere, Marc ;
Dunst, Juergen .
EXPERT REVIEW OF ANTICANCER THERAPY, 2016, 16 (07) :751-758
[4]
Current relevance of hypoxia in head and neck cancer [J].
Bredell, Marius G. ;
Ernst, Jutta ;
El-Kochairi, Ilhem ;
Dahlem, Yuliya ;
Ikenberg, Kristian ;
Schumann, Desiree M. .
ONCOTARGET, 2016, 7 (31) :50781-50804
[5]
CCR7 and CXCR4 as novel biomarkers predicting axillary lymph node metastasis in T1 breast cancer [J].
Cabioglu, N ;
Yazici, MS ;
Arun, B ;
Broglio, KR ;
Hortobagyi, GN ;
Price, JE ;
Sahin, A .
CLINICAL CANCER RESEARCH, 2005, 11 (16) :5686-5693
[6]
Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4 [J].
Cronin, Patricia A. ;
Wang, Jiang H. ;
Redmond, H. Paul .
BMC CANCER, 2010, 10
[7]
Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma [J].
Curry, Joseph M. ;
Sprandio, John ;
Cognetti, David ;
Luginbuhl, Adam ;
Bar-ad, Voichita ;
Pribitkin, Edmund ;
Tuluc, Madalina .
SEMINARS IN ONCOLOGY, 2014, 41 (02) :217-234
[8]
Significance of chemokine and chemokine receptors in head and neck squamous cell carcinoma: A critical review [J].
da Silva, Janine Mayra ;
Soave, Danilo Figueiredo ;
Moreira dos Santos, Talita Pollyanna ;
Batista, Aline Carvalho ;
Russo, Remo Castro ;
Teixeira, Mauro Martins ;
da Silva, Tarcilia Aparecida .
ORAL ONCOLOGY, 2016, 56 :8-16
[9]
Hypoxia-inducible factor 1:: regulation by hypoxic and non-hypoxic activators [J].
Déry, MAC ;
Michaud, MD ;
Richard, DE .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2005, 37 (03) :535-540
[10]
Clinical relevance of the tumor microenvironment and immune escape of oral squamous cell carcinoma [J].
Eckert, Alexander W. ;
Wickenhauser, Claudia ;
Salins, Paul C. ;
Kappler, Matthias ;
Bukur, Juergen ;
Seliger, Barbara .
JOURNAL OF TRANSLATIONAL MEDICINE, 2016, 14