Protease expression in dedifferentiated parosteal osteosarcoma

Background. - Parosteal osteosarcoma with dedifferentiation provides a usef ul model to study tumor progression from an indolent locally aggressive neo plasm to highly lethal metastasizing malignancy. Up-regulation of the prote olytic enzymes participating in stromal degradation is known to promote inv asive growth and metastasis of several human and experimental tumors. Methods. - The expression patterns of urokinasase plasminogen activator (u- PA), its cell-surface receptor (u-PAR), and cathepsin B were analyzed by im munohistochemical techniques in 11 cases of parosteal osteosarcoma and in 4 cases of dedifferentiated parosteal osteosarcoma. Results. - Both enzymes and the receptor were coexpressed in most tumor cel ls of parosteal and dedifferentiated parosteal osteosarcoma. Their expressi on was strikingly enhanced in the dedifferentiated high-grade component of the tumors. Tumor cells involved in bone production (ie, those adjacent to tumor produced bone trabeculae) exhibited equally strong expression of u-PA , u-PAR, and cathepsin B, regardless of their histologic grade. Expression of u-PA, u-PAR, and cathepsin B was undetectable in the "normalized" cells embedded in the well-developed tumor bone trabeculae. Conclusion. - These data indicate that u-PA and its interacting molecules, such as u-PAR and cathepsin B, may have some contributory effects on the me tastatic potential of tumor cells in dedifferentiated parosteal osteosarcom a.