Abstract
Tissue regeneration requires expression of a large, unknown number of genes to initiate and maintain cellular processes such as proliferation, extracellular matrix synthesis, differentiation and migration. A unique model to simulate this process in a controlled manner is the re-growth of the caudal fin of zebrafish after amputation. Within this tissue stem cells differentiate into fibroblasts, epithelial and endothelial cells as well as melanocytes. Many genes implicated in the regeneration process are deregulated in cancer. We therefore undertook a systematic gene expression study to identify genes upregulated during the re-growth of caudal fin tissue. By applying a high stringency cut-off value of 4-fold change, we identified 54 annotated genes significantly overexpressed in regenerating blastema. Further bioinformatics data mining studies showed that 22 out of the 54 regeneration genes where overexpressed in melanoma compared to normal skin or other cancers. Whereas the role of TNC (tenascin C) and FN1 (fibronectin 1) in melanoma development is well documented, implication of MARCKS, RCN3, BAMBI, PEA3/ETV4 and the FK506 family members FKBP7, FKBP10 and FKBP11 in melanoma progression is unclear. Corresponding proteins were detected in melanoma tissue but not in normal skin. High expression of FKBP7, DPYSL5 and MDK was significantly associated with poor survival. We discuss a potential role of these novel melanoma genes, which have promising potential as new therapeutic targets or diagnostic markers.
Highlights
Identification of reliable and specific cancer biomarkers, which would help to diagnose, classify and predict disease outcome is still a challenging task
Since melanocyte differentiation takes place during blastema development and genes participating in this process are deregulated in MM initiation and progression, we determined expression levels of our regeneration genes in public available datasets of melanoma transcriptome studies using Oncomine. 40 percent of the regeneration genes were overexpressed in melanoma, either compared to normal skin (12/54, Figure 2A) or compared to other cancers (10/54; Table 1)
Because of strong relationships between melanocyte differentiation during blastema formation and deregulation of melanocyte differentiation program during melanoma progression [2]
Summary
Identification of reliable and specific cancer biomarkers, which would help to diagnose, classify and predict disease outcome is still a challenging task. This is true for malignant melanoma (MM), because only a small quantity of tissue is available at the time of diagnosis. We found that 40% of the blastema-upregulated genes are overexpressed in melanoma These include known melanomapromoting proteins such as fibronectin and tenascin C [4, 5], and novel promising candidates such as BAMBI, a negative regulator of TGF-beta signaling [6].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
