Bone resorption activity of osteolytic metastatic lung and breast cancers

Production of bone resorption mediators and bone resorption activity were compared among osteolytic metastatic cancers, normal bone tissues, and soft tissue metastatic cancers to search for the possible factors leading to cancer-induced bone resorption. Twenty-five patients with untreated osteolytic metastatic breast or non-small cell lung cancers consisted of the study group. Normal bone tissues obtained from the same patient were used as internal controls; and tumor tissues from patients with soft tissue metastasis were used as external controls. Serum and urinary bone turnover markers were measured. Tissues harvested during surgery were subjected to tissue culture. The levels of prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the supernatant after 72 h of culture were measured. Bone resorption activity was measured by calcium release from cultured calvarias, and bone volume as well as osteoclast number in bone sections. Patients with osteolytic metastatic cancers showed significantly decreased serum osteocalcin, increased serum alkaline phosphatase, and urinary deoxypyridinoline levels. Osteolytic metastatic cancers produced significantly more PGE₂ than both controls. Conditioned medium from osteolytic metastatic tumors showed significantly enhanced bone resorption activity, and indomethacin significantly reduced this activity. Levels of PGE₂, and bone resorption activity increased in osteolytic tumor tissues than soft tissue metastatic tissues in the same patient indicated that the same tumor cells might respond differently to different microenvironments. Our observation showed that PGE₂ was produced by osteolytic metastatic cancers and stimulated bone resorption in mice calvarias. PGE₂ inhibitor may be applicable in reducing bone resorption by osteolytic metastatic cancers.