earticle

영어

Melanoma is an excellent model to study molecular mechanisms of tumor progression because melanoma usually develops through a series of architectural and phenotypically distinct stages that are progressively more aggressive, culminating in highly metastatic cells. In this study, in order to identify the candidate proteins involved in tumor progression and to better understand
key pathways underlying melanoma metastasis, comparative proteome analysis on two melanoma cell strains with low and high metastatic potentials, WM793 and 1205LU, respectively was performed using a 3-D DIGE method consisting of sample Cydyeslabeling, microscale solution isoelectric focusing (MicroSol-IEF) prefractionation, and 2-dimensional differential gel
electrophoresis (2-D DIGE). This method identified 157 protein spots compared with only 15 spots using 2-D DIGE, which showed abundance changes that were both statistically significant and at least 2-fold. Analysis of these gel spots using LCMS/MS resulted in unambiguous identification of the major protein responsible for the observed abundance change in 156 cases.
These 156 identifications represented 110 unique proteins because some spots were different isoforms of the same protein. As expected, some proteins observed in this study were previously linked to metastasis in either melanoma or other tumor types, but in addition, many novel proteins were identified that had not previously been implicated in melaoma metastasis. Most of the novel observed abundance changes closely correlate with biological processes central to cancer progression, such as cell death and growth, and tumorigenesis. In addition, the vast majority of protein changes mapped to six cellular networks, which included known oncogenes (JNK, c-myc, and N-myc) and tumor suppressor genes (p53 and TGF-β) as critical components. These six networks showed substantial connectivity, and most of the major biological functions associated with these pathways are associated with tumor progression. Thus this study led to novel insights into cellular pathway implicated in melanoma metastasis.
[This work was supported by National Institutes of Health Grants CA93372 and CA92725, as well as institutional grants to the Wistar Institute including an NCI Cancer Core Grant (CA10815), and grants from the Pennsylvania Department of Health]