CELLULAR AND HORMONAL MECHANISMS ASSOCIATED WITH MALIGNANT BONE-RESORPTION

BACKGROUND: To obtain a better understanding of the cellular and hormo nal mechanisms responsible for the malignant bone resorption associate d with metastatic carcinoma, we sought to identify whether tumor cells or tumor infiltrating macrophages were capable of lacunar bone resorp tion. EXPERIMENTAL DESIGN: Tumor cells and tumor-infiltrating macropha ges (TIMS), (nonspecific esterase and F4/80 positive: cytokeratin and tartrate-resistant acid phosphatase and calcitonin response negative), were isolated from carcinomas that developed after subcutaneous impla ntation of human breast, colon, and cervical carcinoma cell lines into MFI athymic nude mice. These cells were cultured alone or with stroma l cells on bone slices and evidence of lacunar resorption sought by sc anning electron microscopy. RESULTS: After 7 to 14 days in co-culture with UMR106 osteoblast-like cells in the presence of 1,25-dihydroxy vi tamin D-3, only cells of the TIM population differentiated into osteoc last-like cells (nonspecific esterase-negative: tartrate-resistant aci d phosphatase-positive) capable of extensive lacunar bone resorption. CONCLUSIONS: Cells within the TIM population but not tumor cells are c apable of differentiation into osteoclast-like cells which can resorb bone extensively. Both 1,25 dihydroxyvitamin D-3 and bone stromal cell s are necessary for this to occur. TIM differentiation into cells capa ble of lacunar resorption could account for a component of the extensi ve osteolysis associated with carcinomatous skeletal metastases.