Is Melanoma a stem cell tumor? Identification of neurogenic proteins in trans-differentiated cells

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BioMed Central

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Is Melanoma a stem cell tumor? Identification of neurogenic proteins in trans-differentiated cells Suraiya Rasheed*1, Zisu Mao, Jane MC Chan and Linda S Chan2 Address: 1Laboratory of Viral Oncology and Proteomics Research, Department of Pathology, University of Southern California, 1840 N.Soto St. Los Angeles, CA 90032-3626USA and 2Department of Pediatrics, Keck School of Medicine, University of Southern California, 1840 N. Soto St. Los Angeles, CA 90032-3626, USA Email: Suraiya Rasheed* - [email protected]; Zisu Mao - [email protected]; Jane MC Chan - [email protected]; Linda S Chan - [email protected] * Corresponding author

Published: 22 March 2005 Journal of Translational Medicine 2005, 3:14

doi:10.1186/1479-5876-3-14

Received: 19 January 2005 Accepted: 22 March 2005

This article is available from: http://www.translational-medicine.com/content/3/1/14 © 2005 Rasheed et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background: Although several genes and proteins have been implicated in the development of melanomas, the molecular mechanisms involved in the development of these tumors are not well understood. To gain a better understanding of the relationship between the cell growth, tumorigenesis and differentiation, we have studied a highly malignant cat melanoma cell line that trans-differentiates into neuronal cells after exposure to a feline endogenous retrovirus RD114. Methods: To define the repertoire of proteins responsible for the phenotypic differences between melanoma and its counterpart trans-differentiated neuronal cells we have applied proteomics technology and compared protein profiles of the two cell types and identified differentially expressed proteins by 2D-gel electrophoresis, image analyses and mass spectrometry. Results: The melanoma and trans-differentiated neuronal cells could be distinguished by the presence of distinct sets of proteins in each. Although approximately 60–70% of the expressed proteins were shared between the two cell types, twelve proteins were induced de novo after infection of melanoma cells with RD114 virus in vitro. Expression of these proteins in transdifferentiated cells was significantly associated with concomitant down regulation of growth promoting proteins and up-regulation of neurogenic proteins (p = < 0.001). Based on their physiologic properties, >95% proteins expressed in trans-differentiated cells could be associated with the development, differentiation and regulation of nervous system cells. Conclusion: Our results indicate that the cat melanoma cells have the ability to differentiate into distinct neuronal cell types and they express proteins that are essential for self-renewal. Since melanocytes arise from the neural crest of the embryo, we conclude that this melan