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Cell Fusion and Hyperactive Osteoclastogenesis in Multiple Myeloma

  • Franco SilvestrisEmail author
  • Sabino Ciavarella
  • Sabino Strippoli
  • Franco Dammacco
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 950)

Abstract

Multiple myeloma (MM) is a hematologic malignancy whose progression may account for uncontrolled osteoclastogenesis promoted by the malignant plasma cells within the marrow microenvironment. Osteoclasts are multinucleated cells derived from the fusion of myeloid progenitors such as monocytes/macrophages, in response to specific differentiation factors released within the marrow niche, that are significantly deregulated in MM. In this malignancy DC-STAMP, a major fusogen protein enrolled by pre-osteoclasts, is highly expressed by peripheral macrophages, whereas dendritic cells and myeloma plasma cells show high fusogenic susceptibility and under specific conditions transdifferentiate to osteoclasts. In particular, the malignant plasma cells, besides altered ploidy, expression of cancer stem cell phenotype and high metastasizing capability, are able to express phenotypic markers of osteclasts, namely the proteolytic enzymes for the bone matrix, and to activate the β3 transcriptional pathway leading to ERK1/2 phosphorylation and initiation of the bone resorbing activity. Thus, based on the imbalanced osteoclast formation and activity that involve cells constitutively uncommitted to osteoclast differentiation, both homotypic and heterotypic cell fusions in myeloma marrow microenvironment represent a major pathogenetic event that drives the development and progression of the skeleton devastation typical of the myeloma bone disease.

Keywords

Multiple Myeloma Myeloma Cell Cell Fusion Osteoclast Differentiation Mitotic Catastrophe 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by AIRC, 2009 (Italian Association for Cancer Research), Milan, Italy and by “Biotecnoter” Project funded by “Regione Puglia”, Italy.

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Franco Silvestris
    • 1
    Email author
  • Sabino Ciavarella
    • 2
  • Sabino Strippoli
    • 2
  • Franco Dammacco
    • 2
  1. 1.Department of Internal Medicine and Clinical OncologyUniversity of Bari Medical SchoolBariItaly
  2. 2.Department of Internal Medicine and OncologyUniversity of Bari Medical SchoolBariItaly

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