Prostaglandin E receptor EP4 antagonist suppresses osteolysis due to bone metastasis of mouse malignant melanoma cells.

We examined the effects of prostaglandin E (PGE) receptor subtype EP4 antagonist on bone metastasis of cancer to clarify PGE's role in bone metastasis. Metastatic regions were detected in femurs accompanying severe bone loss in mice injected with B16 malignant melanoma cells. Administration of EP4 antagonist restored the bone loss induced by B16 melanoma. Adding B16 cells induced osteoclast formation in the coculture of bone marrow cells and osteoblasts without any exogenous bone-resorbing factor, and EP4 antagonist completely suppressed the osteoclast formation induced by B16 cells. Therefore, EP4 antagonist is a possible candidate for the therapy of bone metastasis of cancer.