ECTOPIC SECRETION OF OSTEOCALCIN, THE MAJOR NONCOLLAGENOUS BONE PROTEIN, BY THE MYELOMA CELL-LINE NCI-H929

In this study we provide the first evidence that human non-osteoblasti c cells secrete the bone-specific protein osteocalcin, We show that th e myeloma cell line NCI-H929 constitutively produces low amounts of os teocalcin. Furthermore, we demonstrate that this production is strongl y enhanced after 1,25(OH)(2)D-3 stimulation. An amplification or a der egulation of the osteocalcin gene could be responsible for the observe d phenomenon because NCI-H929 has the unusual characteristic of having at least three chromosomes 1, where the osteocalcin gene was mapped ( 1q25-q31), It is of interest to note that the patient in whom the NCI- H929 cell line originated never developed osteolytic lesions despite e xtensive disease apparent at autopsy, Although lytic bone lesions with low osteocalcin serum levels are a common feature of multiple myeloma (MM), a small subset of patients does not develop lytic bone lesions or even demonstrate osteosclerotic MM, This occurrence is associated w ith high osteocalcin serum levels of unknown origin, In this context, osteocalcin production by immortalized tumor lacking any osteolytic po tential could be relevant to the pathophysiology of this particular ty pe of MM.