SP-0016: Head and neck cancer

Abstract

growth factors and tumor oxygenation collaborate to promote EMT and thereby contribute to radioresistance. Since within the tumor microenvironment, a plethora of signaling factors in conjunction with hypoxia may influence EMT induction, we also investigated the role of TGFβ addition or expression of the constitutive EGFRvIII mutant, stimuli known to influence EMT. We have previously shown that EGFRvIII contributes to increased malignancy and others have reported that EGFRvIII expression disrupts adherens junctions and that silencing EGFRvIII reduces expression of factors involved in EMT. Our data indicate that various stimuli emanating from tumor cells or their microenvironment can induce mesenchymal conversion of normal and cancerous epithelial cells. Interestingly, we show that combining these signals results in a more pronounced EMT-like induction. Moreover, EMT-like transformation by the microenvironment is reversible upon reoxygenation. We have correlated these findings with changes in the expression of E-cadherin, and found that cancer cells that express Ecadherin were more sensitive to radiation than their counterparts without E-cadherin. Thus changes in E-cadherin expression in tumors induced by changes in the microenvironment such as hypoxia and reoxygenation may contribute to the intrinsic sensitivity of tumor cells to radiotherapy. Interestingly, in addition to its influence on the process of EMT, our data provide evidence that EGFRvIII over expression promotes autophagy and survival of cancer cells under stress conditions such as hypoxia and starvation. Data on how these observations contribute to radiation resistance will be presented.