Identification of apolipoprotein D as a novel inhibitor of osteopontin-induced neoplastic transformation.

Osteopontin that associates with metabolism of calcium is one of the important factors in the development and prognosis of human breast cancer. The aim of this study was to detect potential binding partners of osteopontin to illustrate its functional mechanism. By screening a human breast cDNA library with a bacterial two-hybrid system, apolipoprotein D was isolated as a novel interacting protein of osteopontin. This interaction was confirmed by mammalian two-hybrid assay and co-immunoprecipitation. To elucidate the influence of ApoD on cellular neoplastic specifications, adhesion, soft agar, invasion and MTT growth assays were performed with Rama37 cells. The results revealed that expression of apolipoprotein D in Rama37 cells could significantly inhibit the malignant phenotype in osteopontin-transformed Rama37 cells. These findings provide better knowledge of the osteopontin signaling pathway and suggest that apolipoprotein D could be a prospective therapeutic agent for human breast and/or other carcinomas.