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Uveal melanoma cell lines and the primary tumors from which they are derived: comparison of their characteristics

ABSTRACT: Development of liver metastasis remains the most common cause of mortality in uveal melanoma (UM). Although advances in genomics allowed the direct evaluation of clinical samples of this eye cancer, there is still a need for reliable preclinical models to progress from correlative studies to mechanistic investigations. A few UM cell lines have been characterized, but so far the translation of basic knowledge to the clinic for the treatment of metastatic disease has been incremental at best. The aim of this study was to determine whether the properties of UM cell lines at various passages were similar to their corresponding primary tumors. Two primary uveal melanoma tumors and their derivative cell lines at three different passages are analyzed by gene profiling

ORGANISM(S): Homo sapiens

SUBMITTER: Zaniolo Karine

PROVIDER: S-ECPF-GEOD-61228 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:BackgroundUveal melanoma is the most common malignancy of the adult eye. The overall mortality rate is high because this aggressive cancer often metastasizes before ophthalmic diagnosis. Quantitative proteomic analysis of primary metastasizing and non-metastasizing tumors was pursued for insights into mechanisms and biomarkers of uveal melanoma metastasis.MethodsEight metastatic and 7 non-metastatic human primary uveal melanoma tumors were analyzed by LC MS/MS iTRAQ technology with Bruch's membrane/choroid complex from normal postmortem eyes as control tissue. Tryptic peptides from tumor and control proteins were labeled with iTRAQ tags, fractionated by cation exchange chromatography, and analyzed by LC MS/MS. Protein identification utilized the Mascot search engine and the human Uni-Prot/Swiss-Protein database with false discovery ≤ 1%; protein quantitation utilized the Mascot weighted average method. Proteins designated differentially expressed exhibited quantitative differences (p ≤ 0.05, t-test) in a training set of five metastatic and five non-metastatic tumors. Logistic regression models developed from the training set were used to classify the metastatic status of five independent tumors.ResultsOf 1644 proteins identified and quantified in 5 metastatic and 5 non-metastatic tumors, 12 proteins were found uniquely in ≥ 3 metastatic tumors, 28 were found significantly elevated and 30 significantly decreased only in metastatic tumors, and 31 were designated differentially expressed between metastatic and non-metastatic tumors. Logistic regression modeling of differentially expressed collagen alpha-3(VI) and heat shock protein beta-1 allowed correct prediction of metastasis status for each of five independent tumor specimens.ConclusionsThe present data provide new clues to molecular differences in metastatic and non-metastatic uveal melanoma tumors. While sample size is limited and validation required, the results support collagen alpha-3(VI) and heat shock protein beta-1 as candidate biomarkers of uveal melanoma metastasis and establish a quantitative proteomic database for uveal melanoma primary tumors.

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Uveal melanoma cell lines and the primary tumors from which they are derived: comparison of their characteristics

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