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.

• Keywords
• IL-6, cancer, cancer ecosystem, cancer microenvironment, cancer therapy, cancer-associated fibroblast, cytokine, extracellular matrix, tumour-associated macrophages,
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Nodular melanoma is one of the most life threatening tumors with still poor therapeutic outcome. Similarly to other tumors, permissive microenvironment is essential for melanoma progression. Features of this microenvironment are arising from molecular crosstalk between the melanoma cells (MC) and the surrounding cell populations in the context of skin tissue. Here, we study the effect of melanoma cells on human primary keratinocytes (HPK). Presence of MC is as an important modulator of the tumor microenvironment and we compare it to the effect of nonmalignant lowly differentiated cells also originating from neural crest (NCSC). METHODS: Comparative morphometrical and immunohistochemical analysis of epidermis surrounding nodular melanoma (n = 100) was performed. Data were compared to results of transcriptome profiling of in vitro models, in which HPK were co-cultured with MC, normal human melanocytes, and NCSC, respectively. Differentially expressed candidate genes were verified by RT-qPCR. Biological activity of candidate proteins was assessed on cultured HPK. RESULTS: Epidermis surrounding nodular melanoma exhibits hyperplastic features in 90% of cases. This hyperplastic region exhibits aberrant suprabasal expression of keratin 14 accompanied by loss of keratin 10. We observe that MC and NCSC are able to increase expression of keratins 8, 14, 19, and vimentin in the co-cultured HPK. This in vitro finding partially correlates with pseudoepitheliomatous hyperplasia observed in melanoma biopsies. We provide evidence of FGF-2, CXCL-1, IL-8, and VEGF-A participation in the activity of melanoma cells on keratinocytes. CONCLUSION: We conclude that the MC are able to influence locally the differentiation pattern of keratinocytes in vivo as well as in vitro. This interaction further highlights the role of intercellular interactions in melanoma. The reciprocal role of activated keratinocytes on biology of melanoma cells shall be verified in the future.

• MeSH
• Cell Differentiation * genetics   MeSH
• Chemokine CXCL1 pharmacology   MeSH
• Adult MeSH
• Epidermal Cells * MeSH
• Epidermis pathology   MeSH
• Fibroblast Growth Factor 2 pharmacology   MeSH
• Interleukin-8 pharmacology   MeSH
• Keratin-10 metabolism   MeSH
• Keratin-14 metabolism   MeSH
• Keratinocytes cytology   drug effects   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Melanocytes metabolism   MeSH
• Melanoma metabolism   pathology   MeSH
• Neoplasm Metastasis MeSH
• Cell Communication * MeSH
• Cell Line, Tumor MeSH
• S100 Proteins metabolism   MeSH
• Aged MeSH
• Gene Expression Profiling MeSH
• Vascular Endothelial Growth Factor A pharmacology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Chemokine CXCL1 MeSH
• Fibroblast Growth Factor 2 MeSH
• Interleukin-8 MeSH
• Keratin-10 MeSH
• Keratin-14 MeSH
• S100 Proteins MeSH
• Vascular Endothelial Growth Factor A MeSH

With the increasing demand for noninvasive approaches in monitoring head and neck cancer, circulating nucleic acids have been shown to be a promising tool. We focused on the global transcriptome of serum samples of head and neck squamous cell carcinoma (HNSCC) patients in comparison with healthy individuals. We compared gene expression patterns of 36 samples. Twenty-four participants including 16 HNSCC patients (from 12 patients we obtained blood samples 1 year posttreatment) and 8 control subjects were recruited. The Illumina HumanWG-6 v3 Expression BeadChip was used to profile and identify the differences in serum mRNA transcriptomes. We found 159 genes to be significantly changed (Storey's P value <0.05) between normal and cancer serum specimens regardless of factors including p53 and B-cell lymphoma family members (Bcl-2, Bcl-XL). In contrast, there was no difference in gene expression between samples obtained before and after surgery in cancer patients. We suggest that microarray analysis of serum cRNA in patients with HNSCC should be suitable for refinement of early stage diagnosis of disease that can be important for development of new personalized strategies in diagnosis and treatment of tumours but is not suitable for monitoring further development of disease.

• MeSH
• Principal Component Analysis MeSH
• Apoptosis genetics   MeSH
• Demography MeSH
• Squamous Cell Carcinoma of Head and Neck MeSH
• Adult MeSH
• Genome, Human genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• RNA, Messenger blood   genetics   MeSH
• Microarray Analysis * MeSH
• Tumor Suppressor Protein p53 metabolism   MeSH
• Head and Neck Neoplasms blood   genetics   pathology   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Aged MeSH
• Signal Transduction genetics   MeSH
• Carcinoma, Squamous Cell blood   genetics   pathology   MeSH
• Gene Expression Profiling MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• RNA, Messenger MeSH
• Tumor Suppressor Protein p53 MeSH