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Coexpression of Bone Sialoprotein (BSP) and the Pivotal Transcriptional Regulator of Osteogenesis, Cbfa1/Runx2, in Malignant Melanoma

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Abstract

Bone sialoprotein (BSP) is a member of the SIBLINGS family, normally restricted to the skeleton, but it has been shown to be ectopically expressed in some human invasive carcinomas. BSP expression in human cancer was initially associated with the ability of BSP-expressing tumors to metastasize to bone, although the mechanism whereby BSP expression should facilitate homing of cancer cells to the bone marrow environment has remained unexplained. More recently, clinical and experimental data have converged in highlighting a potential link between BSP expression and tumor invasiveness in general. We show here that human malignant melanoma cells express BSP in vivo as a function of extent of local invasion, and that expression of BSP mRNA and protein in melanoma cells is associated with the expression of the transcriptional regulator of osteogenic cell differentiation, Cbfa1/Runx2. It has been well established that expression of Cbfa1/Runx2 in the mouse is normally restricted to bone-forming cells. In the mouse, Cbfa1/Runx2 dictates osteogenic differentiation of mesodermal cells by regulating bone-specific genes. Since it also regulates expression of at least two matrix metalloproteases implicated in tumor invasion and metastasis (collagenase 3, membrane type 1 matrix metalloproteinase), we propose that the relationship between BSP expression and an invasive behavior in human epithelial cancer cells may be rooted in a common transcriptional control exerted by Cbfa1.

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Acknowledgements

This work was supported in part by grants from MIUR and AIRC to PB.

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Authors and Affiliations

  1. Department of Experimental Medicine, Laboratory of Pathology, University of L’Aquila, Italy

    M. Riminucci & A. Corsi

  2. Parco Scientifico Biomedico San Raffaele Roma, Rome, Italy

    M. Riminucci & P. Bianco

  3. Department of Biomedical Sciences, Division of Dermatology, University of L’Aquila, Italy

    K. Peris

  4. Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

    L. W. Fisher

  5. Department of Dermatology, Tor Vergata University, Rome, Italy

    S. Chimenti

  6. Department of Experimental Medicine and Pathology, La Sapienza University, Rome, Italy

    A. Corsi & P. Bianco

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  1. M. Riminucci
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  4. L. W. Fisher
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Correspondence to P. Bianco.

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Riminucci, M., Corsi, A., Peris, K. et al. Coexpression of Bone Sialoprotein (BSP) and the Pivotal Transcriptional Regulator of Osteogenesis, Cbfa1/Runx2, in Malignant Melanoma . Calcif Tissue Int 73, 281–289 (2003). https://doi.org/10.1007/s00223-002-2134-y

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