Osteoclast-mediated osteolysis in bone metastasis from renal cell carcinoma

Abstract

Osteolytic characteristics of bone metastasis from renal cell carcinoma were morphologically and biochemically investigated. First, undecalcified ground sections of bone metastases were made from four patients with renal cell carcinoma. Second, renal cell carcinoma cell line (RCC-K1) was established from one of the four patients, and its effect on bone resorption in vitro was examined. Marked proliferation and activation of osteoclasts around the tumor cells was histologically demonstrated. Conditioned medium from the RCC-K1 cells contained potent bone-resorbing activity in vitro. The activity was reduced to basal level by calcitonin, but was not blocked by indomethacin. The activity was lost after dialysis (MW cutoff 3500), while it was retained after 2 weeks of storage. Levels of prostaglandin E2 and 1,25-dihydroxyvitamin D of the RCC-K1-conditioned medium were insufficient to cause bone resorption in vitro. The conditioned medium did not stimulate cAMP accumulation in rat osteoblastic cells. These results suggest that renal cell carcinoma causes bone destruction through the stimulation of osteoclasts by locally secreting an unknown humoral factor or factors.

Distribution of macrophages, osteoclasts and the B-lymphocyte lineage in osteolytic metastasis of mouse mammary carcinoma

“…In osteolytic metastases, osteoclasts play a key role in expanding the borders of metastatic nests (25,37,43). This is supported by histological observations demonstrating osteoclastic bone resorption (2,11,45), as well as by reports that the inhibited osteoclastic activities by the administration of bisphosphonate suppressed osteolysis and subsequent tumor expansion (22,37). As in physiological events, osteoblastic cells appear to regulate osteoclastic activity in the tumor nests through the receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL) system (22).…”

Macrophage Inflammatory Protein–1δ: A Novel Osteoclast Stimulating Factor Secreted by Renal Cell Carcinoma Bone Metastasis

“…Lastly, although we have provided evidence that MIP-1y may influence RBM-induced osteolysis through effects on bone-resorbing osteoclasts, MIP-1y may also have effects on bone-forming osteoblasts. Although evidence suggests that bone loss observed in RBM patients is mediated largely by increased bone destruction (10), reduced bone formation may also play a role. Because osteoblasts express both MIP-1y receptors Figure 3.…”

An orthotopic and osteolytic model with a newly established oral squamous cell carcinoma cell line

“…Previous studies have suggested that bone destruction caused by cancer is mediated by osteoclastic bone resorption rather than directly by tumour cells. 22 However, the mechanism underlying bone invasion remains poorly understood. Thus, the osteolytic model could be used as a reliable model reflecting the cancer-bone environment and has the advantage of accelerating the mechanical demonstration of bone metastasis.…”