The pineal hormone melatonin is also synthesized in the bone marrow, where it induces the formation of osteoblasts and osteoclasts from precursors. Furthermore, it is involved in the modulation of intracellular calcium levels in mature cells. Melatonin has been shown to exert anticancer activity through its antiproliferative action, modulation of oncogene expression, anti-inflammatory and anti-oxidative activities. Therefore, we sought to investigate melatonin receptor expression in primary and/or secondary bone malignancies, and to study melatonin effects in the osteosarcoma cell lines HOS and SaOS. For the expression of melatonin receptors, MT1 and MT2, we analyzed 61 tissue specimens obtained during surgery from patients with primary and secondary (metastatic) malignant tumors of the bone as well as samples from non-malignant bone lesions by RT-PCR. Via these G-protein coupled receptors, melatonin affects PKA and PKC mediated signaling. In the patients’ samples, we found a distinct expression pattern for MT1 and MT2 mRNA. In 30 specimens from primary malignancies (osteosarcomas, chondrosarcomas, Ewing sarcomas) and giant cell tumors, MT1 mRNA was detected in 21 and MT2 mRNA in 17 samples. A similar pattern was seen for non-malignant lesions. In bone cysts (n=11), MT1 mRNA was expressed in 8 and MT2 mRNA in 3 specimens, respectively. 3/8 specimens from patients with scoliosis and exostosis expressed MT1, but not MT2 mRNA. In metastatic lesions from prostate, colon, and kidney tumors (n=12), only MT1 mRNA was detectable at a considerable level, while in bone lesions from a cervix carcinoma, MT2 but not MT1 mRNA was found. Functional studies were performed in HOS cells, in which treatment with 1 μM melatonin has no significant effect on cell growth, although an inhibitory effect of 30% was seen at the pharmacological dose of 100 μM after 3-8 days of treatment. HOS as well as SaOS cells express MT1, but not MT2 mRNA as assessed by RT-PCR. Immunohistochemical staining revealed that MT1 is located at the plasma membrane, although in the majority of cells, nuclear staining is also evident. Our data show that MT1 and MT2 are widely expressed in both, malignant and non-malignant human bone lesions. The divergent MT1 and MT2 expression pattern suggests that their signaling pathways might affect particular targets which could influence the balance between the osteolysis and bone formation in these tumors. Supported by (OEAW DocProg; SA), Hochschuljubiläumsstiftung (H-1033/2004;TT)

[Proc Amer Assoc Cancer Res, Volume 46, 2005]