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3D Sphere cultures of uveal melanoma reveal a molecular signature with a potential target for cancer therapy
Author(s) -
Ness C.,
Garred Ø.,
Eide N.,
Bærland T.,
Nicolaissen B.,
Moe M.,
Noer A.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0679
Subject(s) - malignancy , cancer , cancer research , biology , cancer stem cell , cancer cell , pathology , 3d cell culture , melanoma , immunohistochemistry , population , cell culture , immunology , medicine , genetics , environmental health
Purpose Uveal melanoma ( UM ) is the most common intraocular malignancy and is fatal in approximately 50% of the cases. Cancer relapse can be seen years after treatment. Diverse mechanisms have been proposed to explain the late relapse of UM e.g cancer dormancy and the presence of cancers stem cells ( CSC s). UM has the disadvantage of being difficult to culture, thus a limited number of cell lines are available. 3D sphere cultures of early passages offer a lower degree of clonal selection and perhaps a more accurate reflection of the primary tumours. The propagation of cells as spheres is believed to enrich for a CSC ‐like population. Methods 2D cultures were expanded in RPMI 1640 with 10% FBS , while 3D sphere cultures were expanded in hESC + MEF for 7–10 days. We compared UM primary tumours fresh frozen vs. 2D culture and 3D sphere culture of the same donors by microarray, qRT ‐ PCR , transmission electron microscopy ( TEM ), immunohistochemistry ( IHC ) and chromatin immunoprecipitation (Ch IP ). Results 3D sphere cultures induce signalling pathways that enhance survival and increase oncogenic activity. They show ultrastructural resemblance to in vivo UM s. The metabolic shift seen in 3D cultures could reflect the survival patterns of pre‐metastatic cancer cells. Conclusions The molecular signature of the 3D cultures reveals the presence of attractive targets for future epigenetic modulation or cancer cell vaccines.