Tumor microenvironment – Unknown niche with powerful therapeutic potential

Head and neck squamous cell carcinomas (HNSCC) are in a group of cancers that are the most resistant to treatment. The survival rate of HNSCC patients has been still very low since last 20 years. The existence of relationship between oncogenic and surrounding cells is probably the reason for a poor response to treatment. Fibroblasts are an important element of tumor stroma which increases tumor cells ability to proliferate. Another highly resistance, tumorigenic and metastatic cell population in tumor microenvironment are cancer initiating cells (CICs). The population of cancer initiating cells can be found regardless of differentiation status of cancer and they seem to be crucial for HNSCC development.In this review, we describe the current state of knowledge about HNSCC biological and physiological tumor microenvironment

Different levels of let-7d expression modulate response of FaDu cells to irradiation and chemotherapeutics.

The implication of the let-7 family in cancer development is multifaceted. The family acts as tumor suppressor miRNA although overexpression of let-7 has also been described in many types of cancer, including head and neck squamous cell carcinoma (HNSCC). The aim of this study includes whether different expression levels of let-7d has an influence on chemo- and radiosensitivity. FaDu cell line models with a gradually increased level of let-7d (models from A to E) were generated with the lentiviral system. Expression levels of pluripotency, chemo-radioresistance/apoptosis, and targets of mRNAs were analyzed by real-time reverse transcription-PCR (qRT-PCR). Radiosensitivity was analyzed using a clonogenic assay after irradiation. Response to cisplatin, 5-FU, doxorubicin, and paclitaxel was done with MTT assay. Statistically significant decrease of K-RAS (p = 0.0369) and CASPASE3 (p = 0.0342) were observed with the growing expression level of let-7d. Cisplatin, 5-FU and doxorubicin caused similar decreased of cell survival with the increase of let-7d level (p = 0.004, post-trend p = 0.046; p = 0.004, post trend p = 0.0005 and p<0.0001, post trend p = 0.0001, respectively). All models were resistant to paclitaxel, irrespective of let-7d expression levels. Only two of the generated models (A and C) were radiosensitive (p = 0.0002). CONCLUSION:the above results indicated that the level of let-7d expression is an important factor for cell response to irradiation and chemotherapeutics

Response of FaDu let-7d models to chemo-and radiotherapy.

<p>A) The cell line models (A-E) were exposed to chemotherapeutics: cisplatin (1.12 μg/mL); 5-FU (0.86 μg/mL); paclitaxel (0.54 μM), and doxorubicin (0.06 μM) were compared to FaDu-GFP B) Survival fractions [SF%] of the cell models were assessed according to a dose of 2 Gy. The differences in survival were statistical significant (<i>p</i> = 0.0002) for the models A and C.</p

Expression of genes characteristic for.

<p>A) pluripotency (OCT3/4, SOX2, NANOG) and B) let-7d targets: K-RAS, Caspase3, H-RAS, N-RAS, HMGA1, HMGA2, C-MYC, ARIDA3A, DICER; C) genes connected with chemo-radioresistance/apoptosis (BAX, ATM, ABCB1, BCL2); D) statistical analysis of models B-E indicated positive results for mRNAs: Caspase3, ATM, K-RAS, N-RAS, HMGA1, and ARID3A.</p