Abstract 66: MHC class I polypeptide related sequence A as contributing factor to chemotherapy-induced resistance

MHC class I polypeptide related sequence A (MICA) is a cell surface protein associated to tumor immunosurveillance activity, due to its ability to activate natural killer (NK) cells. Cleavage of MICA and generation of its soluble form (sMICA) has been described as an immunoevasion mechanism presented by aggressive tumors. In agreement with the role of MICA on tumor immunoevasion, recent studies correlated better prognosis for patients with higher levels of MICA expression in different types of cancer. Chemotherapeutic drugs are used to treat a great variety of malignant diseases. However, a fraction of patients under chemotherapy regimen stop responding to the treatment and develop recurrent tumors. We postulate that MICA can be a factor contributing to chemotherapy-induced resistance. To test our hypothesis, we tested the expression of MICA in prostate cancer-derived LNCaP and E006AA-hT cell lines were treated with bortezomib, a chemotherapeutic drug that inhibits proteasome activity. MTT cell viability assays showed that both cells had similar sensitivity to bortezomib, with IC50 of 10 nM and 8 nM for LNCaP and E006AA-hT, respectively. Flow cytometry analysis showed baseline difference in the cell fraction expressing surface MICA with 67% in LNCaP cells against 18% in E006AA-hT (p