Analyse der Expression von Chemokinen und Chemokinrezeptoren in Kopf-Hals-Tumorzellen

Radiotherapy plays an important role in the treatment of malignant head and neck tumors. Chemokines are chemotactic cytokines, which can induce tumor proliferation as well as metastasis, although the influence of chemokines and their signaling pathways via chemokine receptors is not fully understood. Moreover, the radiation-induced expression of chemokines and chemokine receptors is poorly studied. Therefore, the purpose of this work was to analyze the expression of the chemokines of the CC-and CXC-class and their receptors in untreated and in irradiated squamous cell carcinoma of the head and neck (SCCHN). The expression of chemokines and chemokine receptors in 15 head and neck carcinoma cell lines and two normal tissue cell lines was analyzed. The spontaneous expression and the expression 6 hours after irradiation with 2 Gy was determined. To validate the results, certain chemokines and chemokine receptors were re-analyzed in selected cell lines. In this second independent analysis the expression was detected for 48 hours after irradiation. Gene expression of chemokines and their receptors was detected by real-time PCR. In addition, the protein expression of two chemokines was analyzed by ELISA. The results of the first analysis showed, that the chemokine receptors were less widely expressed in the investigated cell lines than the chemokines. Irradiation with 2 Gy caused an altered expression of the chemokines and chemokine receptors in all investigated cell lines. Radiation caused up- and downregulation in the expression of the chemokines, whereas the expression of the investigated receptors was predominantly downregulated after irradiation. The results of the chemokine expression were validated in the second, independent analysis. Radiation caused again up- and downregulation in the expression of the chemokines, but also showed that the expression of the chemokines and its receptors varies over the entire period of 48 hours after irradiation. The protein expression of the chemokines CXCL1 and CXCL12 corresponded well with the mRNA expression. In summary, irradiation of squamous cell carcinoma of the head and neck (SCCHN) and normal tissue cells caused a radiation-induced change of gene expression of the chemokine and its receptors. The results of this analysis show the complexity of the topic, so further studies will be needed to fully understand the influence of chemokines and chemokine receptors and their effect under a treatment of squamous cell carcinoma of the head and neck.