Activation of the STAT3 signaling pathway in Metastatic Uveal Melanoma

Abstract

Purpose : Purpose: Determine whether the metastatic UM cell line OMM2.5 shows high STAT3 activation as compared to non-metastatic UM cell line MEL270 derived from the same UM patient. Does the OM2.5 cell line express more immunosuppressive chemokines/cytokines, and/or less inflammatory cytokines/chemokines.

Methods : Methods: The proliferation of OMM2.5 and MEL270 UM cell lines was determined by IncuCyte Live-Cell Analysis assays. The levels of STAT3 and tyrosine phosphorylated STAT3 in cell lysates was determined by immunoblotting. The expression of STAT3-depedent chemokines and cytokines was compared in MEL270 versus OMM2.5 cells by quantitative real time PCR.

Results : Results: The metastatic UM cell line OMM2.5 cell line showed increased cell proliferation compared to the primary MEL270 UM cells isolated from the same patient. In addition, STAT3 activation was markedly elevated as evidenced by its tyrosine phosphorylation in the metastatic OMM2.5 cell line relative to MEL270 UM cells. Moreover, the gene expression levels of multiple STAT3 regulated genes, such as STAT1, TXNIP, and LIF was significantly increased in metastatic OMM2.5 cells vs. non-metastatic MEL270 UM cells. LIF (leukemia inhibitory factor) is a cytokine that plays a key role in regulating the adaptive immune response. TXNIP (Thioredoxin-interacting protein) is a redox regulator that causes accumulation of reactive oxygen species, and has been associated with tumorigenesis in several cancer. STAT1 is a transcription factor that promotes oncogenesis in various cancer types.

Conclusions : Conclusions: Taken together, these data indicate that the STAT3 signaling pathway is activated in metastatic uveal melanoma cell lines. Thus, STAT3 may be an attractive pharmacological target to treat metastatic uveal melanoma.

This is a 2021 ARVO Annual Meeting abstract.