Bidirectional cross talk between uveal melanoma cells and hepatic myofibroblasts promotes inflammation‐induced chemokines expression

Abstract

PurposeUveal melanoma (UM) is the most common primary ocular neoplasm in adults. Its cause is largely unknown, and no risk factors have yet been identified. The metastatic disease develops in up to 50% of patients, usually involving the liver. Treatment only rarely prolongs survival, because metastases are highly resistant to most chemotherapeutic agents. Tumor cells may modulate the functions of surrounding cells to facilitate their own growth, survival, invasion, and metastasis. This study was conducted to investigate the role of hepatic microenvironment on UM cells (UMC).MethodsHere, we utilized metastatic (Omm2.3) and non‐metastatic (Mel270) UMC in coculture with hepatocyte‐stellate cells (HSC) LX2. The transcriptomic study was performed by microarray assay. Expression of relevant genes was measured by qPCR. Cytokines were quantified by Elisa test. Cell proliferation was assessed by MTT staining. Extracellular matrix components were evaluated by quantitative cell adhesion assay.ResultsHepatic microenvironment increased the expression of numerous genes. However, the number of genes overexpressed in metastatic co‐cultures is three‐times higher than in non‐metastatic cocultures, demonstrating that hepatic microenvironment has more impact on metastatic UMC. Over‐expressed genes in coculture were linked to inflammation and included several interleukins. In addition, UMC‐HSC crosstalk generated expression of cell adhesion receptors, particularly by increasing fibronectin. In contrast, hepatic microenvironment had no effect on cell proliferation.ConclusionsOur results provide evidence for an important role of inflammation in the progression of metastatic UM. Therefore, the inflammatory characteristics of the tumor microenvironment might offer therapeutic opportunities.