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

Suraiya Rasheed,Jane Mc Chan,Zisu Mao,Linda S Chan

doi:10.1186/1479-5876-3-14

Suraiya Rasheed, Jane Mc Chan + Show 2 more

Open Access

https://doi.org/10.1186/1479-5876-3-14

Copy DOI

Abstract

BackgroundAlthough 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.MethodsTo 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.ResultsThe 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 trans-differentiated 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.ConclusionOur 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 melanoma arose from embryonic precursor stem cells. This model system provides a unique opportunity to identify domains of interactions between the expressed proteins that halt the tumorigenic potential of melanoma cells and drive them toward neurogenerative pathways involved in early neurogenesis. A better understanding of these proteins in a well-coordinated signaling network would also help in developing novel approaches for suppression of highly malignant tumors that arise from stem-like embryonic cells.

Highlights

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 mechanisms involved in the growth, differentiation and transformation of cells, we have studied a fully differentiated highly malignant cat melanoma cell line CT1413, that trans-differentiates into neuronal cells, 48–72 hours after infection with the endogenous cat retrovirus RD114 in vitro [2,3]
We have shown that RD114 virus infection of cat melanoma cells induces a repertoire of novel proteins that

Summary

Introduction

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. The trans-differentiated cells exhibit long multipolar cytoplasmic extensions that form a network of connections with giant multinucleated neuronal cells and smaller glial-like cells (Fig. 1A, B &1C). This transformation is a highly specific event for CT1413 cells and its interaction with RD114 virus since no morphological change occurs when these cells are treated with various chemicals known to induce cell differentiation (dexamethasone, insulin, isobutyl-methyl-xathine) or they are infected separately with primate retroviruses that use the same neutral amino acid (NAA) transporter proteins as receptors as does RD114 virus [4,3].

Methods

Results

Conclusion