Abstract:
:Uveal melanoma is associated with a high tumor-related mortality due to the propensity to develop metastases. The mechanisms that are responsible for malignant dissemination are largely unknown and need to be explored to facilitate diagnosis and treatment of metastases. To identify molecules involved in dissemination, we used cell lines derived from a primary uveal melanoma and 2 liver metastases from the same patient as a model for tumor progression. Using a microarray representing 1,176 genes, we identified 63 differentially expressed genes. Forty genes showed a higher expression and 23 showed a lower expression in the primary cell line compared to the metastasis cell lines. These genes are involved in processes like angiogenesis, apoptosis, macrophage stimulation, and extracellular matrix regulation. In contrast, the 2 liver metastasis cell lines produced nearly identical expression profiles. Demethylation of the primary melanoma cell line by 5-aza-2'deoxycytidine treatment revealed that 19 genes were suppressed by hypermethylation. An important finding was the 5-fold decreased expression of TIMP3 in the metastatic cell lines, a molecule involved in extracellular matrix degradation. We demonstrate in the cell lines that TIMP3 expression is regulated by methylation. These observations were confirmed in primary uveal melanoma and suggests a role for TIMP3 in uveal melanoma development.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
van der Velden PA,Zuidervaart W,Hurks MH,Pavey S,Ksander BR,Krijgsman E,Frants RR,Tensen CP,Willemze R,Jager MJ,Gruis NAdoi
10.1002/ijc.11262keywords:
subject
Has Abstractpub_date
2003-09-10 00:00:00pages
472-9issue
4eissn
0020-7136issn
1097-0215journal_volume
106pub_type
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