[Bone metastasis by renal cell carcinoma. Importance of calcium and calcium-sensing receptor]

Abstract

Bone tissue is one of the main locations of metastases in renal cell carcinoma (RCC). In bone tissue the concentration of calcium ions is very high. Cells recognize extracellular calcium by the calcium-sensing receptor (CaSR). To investigate the role of calcium in bone metastases, the CaSR was quantified in tumor tissue and primary tumor cells of patients who were free of metastases or developed bone or lung metastases during a time period of 5 years after nephrectomy. In tissue specimens and primary cells of patients developing bone metastases, CaSR expression was clearly enhanced. Functionally, analyses showed a higher sensitivity in bone metastasizing cells concerning proliferation and chemotactical migration. These effects were caused by enhanced activity of the downstream targets of CaSR, namely AKT, PLCg, JNK and p38, analyzed in a phospho-kinase array and western blot analysis. The extent to which CaSR is suitable as a new marker for bone-specific metastases from renal cancer must be examined further.