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BACKGROUND: To obtain a better understanding of the cellular and hormonal mechanisms responsible for the malignant bone resorption associated with metastatic carcinoma, we sought to identify whether tumor cells or tumor infiltrating macrophages were capable of lacunar bone resorption. EXPERIMENTAL DESIGN: Tumor cells and tumor-infiltrating macrophages (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 implantation of human breast, colon, and cervical carcinoma cell lines into MFI athymic nude mice. These cells were cultured alone or with stromal cells on bone slices and evidence of lacunar resorption sought by scanning electron microscopy. RESULTS: After 7 to 14 days in co-culture with UMR106 osteoblast-like cells in the presence of 1,25-dihydroxy vitamin D3, only cells of the TIM population differentiated into osteoclast-like cells (nonspecific esterase-negative: tartrate-resistant acid phosphatase-positive) capable of extensive lacunar bone resorption. CONCLUSIONS: Cells within the TIM population but not tumor cells are capable of differentiation into osteoclast-like cells which can resorb bone extensively. Both 1,25 dihydroxyvitamin D3 and bone stromal cells are necessary for this to occur. TIM differentiation into cells capable of lacunar resorption could account for a component of the extensive osteolysis associated with carcinomatous skeletal metastases.

Type

Journal article

Journal

Laboratory investigation; a journal of technical methods and pathology

Publication Date

10/1994

Volume

71

Pages

465 - 471

Addresses

University of Oxford, Nuffield Department of Pathology and Bacteriology, John Radcliffe Hospital.

Keywords

Cells, Cultured, Tumor Cells, Cultured, Macrophages, Osteoclasts, Osteoblasts, Animals, Humans, Mice, Mice, Nude, Adenocarcinoma, Carcinoma, Squamous Cell, Breast Neoplasms, Colonic Neoplasms, Bone Resorption, Calcitriol, Calcitonin, Microscopy, Electron, Scanning, Immunohistochemistry, Neoplasm Transplantation, Cell Differentiation, Time Factors, Uterine Cervical Neoplasms, Female, Keratins