Identification of Markers Associated with Highly Aggressive Metastatic Phenotypes Using Quantitative Comparative Proteomics

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The spread of cancer cells from a primary tumor to form metastases at distant sites is a complex process that remains poorly defined. Certain tumor cells are more aggressive and thus lead to rapid development of multiple distant metastases. Here we identify proteins associated with these aggressive phenotypes. To identify proteins associated with cancer cell aggressiveness, we used comparative quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteome analysis of a unique metastasis model comprised of three isogenic human breast cancer cell lines that are equally tumorigenic in mice, but display different metastatic potentials ranging from non-metastatic, intermediate metastatic and highly metastatic. The difference in metastatic capabilities was initially confirmed using live animal imaging. Comparative quantitative proteomics identified 414 proteins, of which 44 exhibited altered expression between the metastatic and non-metastatic cell lines. The proteins correlating with the aggressiveness of metastasis included leucine-rich repeat containing protein 59 (LRRC59), while CD59 and chondroitin sulfate proteoglycan 4 (CSPG4) exhibited an inverse correlation with metastatic capability. The altered expression levels of these proteins were biochemically confirmed as well as demonstrated in xenografts generated from these cell lines. This analysis further demonstrated that the three proteins were associated with the aggressiveness of metastasis rather than metastasis colonization per se. Our study provides novel insights into key proteins associated with the metastatic potential of breast cancer cells and identified LRRC59, CD59 and CSPG4 as candidates that merit further study.
Original languageEnglish
Publication date29. Nov 2012
Publication statusPublished - 29. Nov 2012
Event7th International Conference on Genomics & Bio-IT APAC 2012 - Hong Kong, China
Duration: 28. Nov 20121. Dec 2012


Conference7th International Conference on Genomics & Bio-IT APAC 2012
CityHong Kong

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