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Cell Fusion and Hyperactive Osteoclastogenesis in Multiple Myeloma

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Cell Fusion in Health and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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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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Authors and Affiliations

  1. Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, 70124, Bari, Italy

    Franco Silvestris

  2. Department of Internal Medicine and Oncology, University of Bari Medical School, 70124, Bari, Italy

    Sabino Ciavarella, Sabino Strippoli & Franco Dammacco

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  1. Franco Silvestris
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  2. Sabino Ciavarella
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Correspondence to Franco Silvestris .

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  1. Inst. Immunologie, Universität Witten/Herdecke, Stockumer Str. 10, Witten, 58448, Germany

    Thomas Dittmar

  2. Institute of Immunologie, University of Witten/Herdecke, Stockumer Str. 10, Witten, 58448, Germany

    Kurt S. Zänker

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Silvestris, F., Ciavarella, S., Strippoli, S., Dammacco, F. (2011). Cell Fusion and Hyperactive Osteoclastogenesis in Multiple Myeloma. In: Dittmar, T., Zänker, K. (eds) Cell Fusion in Health and Disease. Advances in Experimental Medicine and Biology, vol 950. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0782-5_5

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