Inflammation-induced chemokine expression in uveal melanoma cell lines stimulates monocyte chemotaxis

ABSTRACT: Purpose: Uveal melanoma (UM) is the most common primary intraocular tumor in adults and the presence of infiltrating leucocytes is associated with a poor prognosis. Little is known how infiltrating leucocytes influence the tumor cells. The purpose of this study was to investigate the effect of activated T cells on the expression of chemotactic cytokines in UM cells. Furthermore, we examined the ability of stimulated UM cells to attract monocytes. Methods: We used an in vitro co-culture system in which UM cell lines and T cells were cultured together, but separated by a membrane. UM gene expression was quantified using a microarray. Protein expression in the supernatant was quantified with ELISA or cytometric bead array. For the monocyte migration assay, a trans-well plate was used. Results: Gene-expression analysis of UM cell lines showed that co-culture with activated T cells resulted in an upregulation of chemokines such as CXCL8, CXCL9, CXCL10, CXCL11, CCL2, CCL5, vascular endothelial growth factor (VEGF), intracellular adhesion molecule 1 (ICAM1) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The upregulation of these molecules was confirmed at the protein level. This increase of chemokines coincided with an increased chemotactic capacity of the supernatant towards monocytes. Conclusions: Cytokines derived from activated T cells shifted the UM cell-transcriptome towards a more inflammatory state, including upregulation of several chemokines, which led to an increased migration of monocytes. Therefore, UM cells might actively participate in generating a tumor- promoting inflammatory microenvironment. One replicate for each cell lines (92.1, Mel 270 and Mel 290) was analyzed before and after co-culture with activated T cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Jehs Tina 

PROVIDER: S-ECPF-GEOD-55983 | biostudies-other |

REPOSITORIES: biostudies-other