RUOLO DELL'ERITROPOIETINA (EPO) NELLA RISPOSTA A RADIAZIONI DA PARTE DI TUMORE TESTA-COLLO

Erythropoietin (EPO) is used commonly to treat cancer and/or therapy-related anaemia. Until recently, EPO was considered to be a specific stimulator of erythropoiesis, acting via its receptor, EPOR. It becomes clear, however, that EPOR is expressed in a variety of cell types other than haematopoietic cells, and that EPO is a potent cytoprotective cytokine increasing cell survival under hypoxic conditions. EPO and EPOR are also expressed in various malignant tumours, and EPOR expression shows association with tumour invasion and progression. It is well known that the radio sensitivity of tumour cells can be significantly reduced under hypoxic condition and that the benefits of radiotherapy in cancer decrease when anaemia is present. Head and Neck Carcinoma (HNC) is comprised of a heterogeneous group of tumours arising from the epithelial lining of the oral cavity, pharynx and larynx and it is the sixth most common cancer world-wide. Despite their heterogeneity, Head and Neck Carcinoma share several features that make them an ideal model for assessing the impact of anaemia and tumour hypoxia on the response to radiation therapy: they are predominantly loco regional in nature, thus providing a therapeutic opportunity in which improvements in local control are likely to directly improve survival. In addition, a substantial body of evidence suggests that tumour hypoxia is common in head and neck tumours and some authors reported that a correlation exists between hypoxia in the tumours and anaemia in patients who present with these cancers. The purpose of the present study was to establish an experimental model and to provide experimental evidences to examine the relationship between hypoxia, EPO/EPOR and EGFR transcription/expression and their effects on the cellular response to radiation. We analyzed the possibility that EPO, EPOR and EGFR expression may contribute to the survival of HNC cells underwent hypoxic conditions by studying the hypoxic regulation of these proteins and other key molecular markers in our cell lines (CAL166). We concluded that the expression of the EPOR in Cal-166 cells does not seem essential for their growth and that administration of EPO does not affect RT efficacy. These results show that recombinant epoetins do not evoke a physiologic response on EPOR- bearing tumour cells as assessed by cellular growth and proliferation.