Osteoclast-like transformation of cultured human myeloma cell lines depends on RANK-L stimulation

08-24-2006

"Hyperactive osteoclastogenesis is a hallmark of multiple myeloma, a B cell neoplasia homing to bone marrow and resulting in multiple osteolytic lesions and skeleton devastation. We provide evidence that myeloma cells can themselves act as osteoclasts in vitro," investigators in Italy reported.

"By extending standard cultures of U-266 and MCC-2 myeloma cell lines, we found that subsets of adherent cells also expressed the osteoclast phenotype, including multinuclear morphology, cytoplasmic tartrate-resistant acid phosphatase, the calcitonin receptor and a specific osteoclast antigen. These subsets resorbed bone substrates by producing osteoclast enzymes as well as the characteristic redistribution of F-actin in their cytoskeleton, thus forming the sealing zone that is adopted by adherent osteoclasts to generate the acidified environment essential for bone resorption," explained N. Calvani and colleagues, University of Bari.

"Neither the phenotype nor the functional properties of osteoclasts were detected in parental non-adherent cells. In adherent cultures osteoclastogenesis was associated with deregulated expression of both receptor activator of nuclear transcription factor (NF)-kappa B (RANK) and its ligand RANK-L, which triggers cell maturation in osteoclast precursors. Resorption of bone substrates was prevented by a neutralizing anti-RANK-L antibody."

The researchers concluded, "Our data indicate that osteoclast-like transformation of both U-266 and MCC-2 cellular models of human myeloma is dependent on RANK-L stimulation."

Calvani and colleagues published their study in British Journal of Haematology (Functional osteoclast-like transformation of cultured human myeloma cell lines. Br J Haematol, 2005;130(6):926-938).

For additional information, contact F. Silvestris, University of Bari, Dept. Internal Medicine & Clinic Oncology, Piazza Giulio Cesare 11, I-70124 Bari, Italy.

Keywords: Bari, Italy, Bone Marrow, F Actin, Multiple Myeloma, Neurology, Oncology, Osteoclasts, Phosphatase, Receptor Activator, Nuclear Transcription Factor Kappa B, Receptor Activator, Nuclear Transcription Factor, NF-Kappa B, Osteoclast-Like Transformation, U-266, MCC-2 Cellular, RANK-L Stimulation.

This article was prepared by Cancer Gene Therapy Week editors from staff and other reports. Copyright 2006, Cancer Gene Therapy Week via NewsRx.com.