The Head and Neck Squamous Cell Carcinoma Microenvironment as a Potential Target for Cancer Therapy

Similarly to other types of malignant tumours, the incidence of head and neck cancer is increasing globally. It is frequently associated with smoking and alcohol abuse, and in a broader sense also with prolonged exposure to these factors during ageing. A higher incidence of tumours observed in younger populations without a history of alcohol and tobacco abuse may be due to HPV infection. Malignant tumours form an intricate ecosystem of cancer cells, fibroblasts, blood/lymphatic capillaries and infiltrating immune cells. This dynamic system, the tumour microenvironment, has a significant impact on the biological properties of cancer cells. The microenvironment participates in the control of local aggressiveness of cancer cells, their growth, and their consequent migration to lymph nodes and distant organs during metastatic spread. In cancers originating from squamous epithelium, a similarity was demonstrated between the cancer microenvironment and healing wounds. In this review, we focus on the specificity of the microenvironment of head and neck cancer with emphasis on the mechanism of intercellular crosstalk manipulation for potential therapeutic application.

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Ionizing radiation affects the composition of the proteome of extracellular vesicles released by head-and-neck cancer cells in vitro

Journal of Radiation Research ◽

10.1093/jrr/rrz001 ◽

2019 ◽

Vol 60 (3) ◽

pp. 289-297 ◽

Cited By ~ 17

Author(s):

Agata Abramowicz ◽

Anna Wojakowska ◽

Lukasz Marczak ◽

Malgorzata Lysek-Gladysinska ◽

Mateusz Smolarz ◽

...

Keyword(s):

Head And Neck Cancer ◽

Ionizing Radiation ◽

Head And Neck ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Neck Cancer

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IGF-1R-Mediated Resistance to EGFR Kinase Inhibitor PD158780 in Head and Neck Cancer Cells

Otolaryngology ◽

10.1016/j.otohns.2005.05.200 ◽

2005 ◽

Vol 133 (2) ◽

pp. P95-P95

Author(s):

M JAMESON ◽

A BECKLER ◽

L SANDSTROM ◽

C THOMAS ◽

P LEVINE

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Cells ◽

Neck Cancer ◽

Kinase Inhibitor ◽

Egfr Kinase

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Mitochondrial pyruvate carrier 1 regulates ferroptosis in drug-tolerant persister head and neck cancer cells via epithelial-mesenchymal transition

Cancer Letters ◽

10.1016/j.canlet.2021.03.013 ◽

2021 ◽

Author(s):

Ji Hyeon You ◽

Jaewang Lee ◽

Jong-Lyel Roh

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Cells ◽

Neck Cancer ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Mitochondrial Pyruvate Carrier

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The complement receptors CD46, CD55 and CD59 are regulated by the tumour microenvironment of head and neck cancer to facilitate escape of complement attack

European Journal of Cancer ◽

10.1016/j.ejca.2014.05.005 ◽

2014 ◽

Vol 50 (12) ◽

pp. 2152-2161 ◽

Cited By ~ 24

Author(s):

Rebecca Kesselring ◽

Annette Thiel ◽

Ralph Pries ◽

Stefan Fichtner-Feigl ◽

Stefan Brunner ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Tumour Microenvironment ◽

Complement Receptors

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TLR3 agonists improve the immunostimulatory potential of cetuximab against EGFR+head and neck cancer cells

OncoImmunology ◽

10.4161/onci.24677 ◽

2013 ◽

Vol 2 (6) ◽

pp. e24677 ◽

Cited By ~ 31

Author(s):

Chwee Ming Lim ◽

Ryan Stephenson ◽

Andres M Salazar ◽

Robert L Ferris

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Cells ◽

Neck Cancer

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Down-regulation of multiple cell survival proteins in head and neck cancer cells by an apoptogenic mutant of adenovirus type 5

Virology ◽

10.1016/j.virol.2009.06.048 ◽

2009 ◽

Vol 392 (1) ◽

pp. 62-72 ◽

Cited By ~ 5

Author(s):

S. Vijayalingam ◽

T. Subramanian ◽

Jan Ryerse ◽

Mark Varvares ◽

G. Chinnadurai

Keyword(s):

Head And Neck Cancer ◽

Cell Survival ◽

Head And Neck ◽

Cancer Cells ◽

Neck Cancer ◽

Adenovirus Type ◽

Down Regulation ◽

Multiple Cell ◽

Adenovirus Type 5 ◽

Survival Proteins

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Head and neck cancer cells and xenografts are very sensitive to palytoxin: decrease of c-jun n-terminale kinase-3 expression enhances palytoxin toxicity

Molecular Cancer ◽

10.1186/1476-4598-12-12 ◽

2013 ◽

Vol 12 (1) ◽

pp. 12 ◽

Cited By ~ 12

Author(s):

Tibor Görögh ◽

László Bèress ◽

Elgar S Quabius ◽

Petra Ambrosch ◽

Markus Hoffmann

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Cells ◽

Neck Cancer

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NF-κB1 intronic region polymorphisms as risk factor for head and neck cancer in HPV-infected population from Pakistan

Current Molecular Medicine ◽

10.2174/1566524021666210302144344 ◽

2021 ◽

Vol 21 ◽

Author(s):

Sumaira Sarwar ◽

Muammad Usman Tareen ◽

Maimoona Sabir ◽

Aneesa Sultan ◽

Salman A Malik

Keyword(s):

Head And Neck Cancer ◽

Lymph Nodes ◽

Head And Neck ◽

Tobacco Use ◽

Neck Cancer ◽

Direct Sequencing ◽

Hpv Infection ◽

Pakistani Population ◽

Specific Pcr ◽

Increased Risk

Background: Head and neck cancer (HNC) developed due to the number of risk factors, including infection of Human Papillomavirus (HPV). The genetic predisposition also plays an important role in deregulating the NF-κB pathway, and certain polymorphisms are reported to affect the pathway genes. Objectives: The present study was conducted for the detection of HPV and polymorphisms in the NF-κB1 gene of HNC patients in the Pakistani population. Methods: Genomic DNA from HNC tumors samples were extracted using the Exgene SV DNA extraction Kit. Allele-specific PCR and direct sequencing were done for analysis of NF-κB1 SNPs, 94ins/del (rs28362491), rs1598858, and rs4648068. Results: The genotypes AG (36.2%/ 12%) of rs1598858, and AG (28.3%/ 12%) and GG (28.3%/ 22%) of rs4648068 were associated with significantly (p≤0.05) increased risk of head and neck cancer in studied population. Furthermore, among the HNC cases, genotypes AGrs1598858 (p≤0.014) and GGrs4648068 (p≤0.001) had increased risk of HPV related cancers. Tobacco use (OR-3.158442; [1.140, 8.754]), lymph nodes involvement (OR 4.05128; [1.854, 8.852]), and poorly differentiated tumors (OR 1.997155; [0.940, 4.245]) were positively associated with HPV induced cancers. Conclusion: It was the first comprehensive study from Pakistan, to evaluate the polymorphic variants of NF-κB1. Genotypes AGrs4648068, GGrs4648068, and AGrs1598858 of NF-κB1 gene are associated with increased risk of head and neck cancers in the Pakistani population. It can be concluded that HPV infection, lymph nodes and tobacco use can act synergetic to each other and add up in modulating HNC when present together with intronic SNPs of NF-κB1 gene.

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