Prevalent expression of MHC class I chain-related molecule A in human osteosarcoma. MHC class I chain-related molecule A (MICA) is one of the major ligands for activating immune-receptor NKG2D which is expressed on NK cells and cytotoxic T lymphocytes. The release and sustained expression of MICA protein can impair NKG2D-mediated cytotoxic activity by reducing NKG2D receptor on immune effector cells. The aim of the study was to investigate the expression and release of MICA in human osteosarcoma. RT-PCR, immunohistochemistry, western blotting and flow cytometry were used in analyzing the expression of MICA. Serum level of soluble MICA was quantitated by ELISA. Our data showed that MICA is prevalently expressed in osteosarcoma both in mRNA and protein level. Upregulation of MICA was found in osteosarcoma compared with benign tumors and normal bone tissues. Higher level of soluble MICA in serum can be detected in osteosarcoma patients. In conclusion, prevalent expression of MICA and higher serum level of soluble MICA may suggest a deficiency of MICA-NKG2D mediated immunosurveillance in osteosarcoma patients. Restoring the expression of NKG2D receptor on immune effector cells may contribute to a therapeutic strategy for human osteosarcoma.