Constitutive expression and roles of interleukin-8 in canine hemangiosarcoma

Results IL-8 mRNA expression was variable among the tissue samples and both IL-8 mRNA and protein were variable among the cell lines. In contrast, IL-8 receptor mRNA and protein showed minimal variance. “IL-8 high” and “IL-8 low” groups were defined from the HSA tumor samples based on gene expression profiles. The “IL-8 high” group was associated with a “reactive microenvironment,” showing enrichment of coagulation, inflammation, and fibrosis networks. However, IL-8 added exogenously and IL-8 blockade using neutralizing antibodies had no effect on HSA cell proliferation, despite apparent response to these signals at the level of gene expression. Similarly, neither addition nor blockade of IL-8 protected cells from apoptosis. IL-8 mRNA was elevated in HSA cancer stem cells, but exogenous IL-8 attenuated self-renewal of these cells. Conclusion The results of this study suggest that IL-8 is a driver of tumor heterogeneity, steering cells away from self-renewal and towards partial differentiation. It also could act to recruit (or produce from the tumor) inflammatory and pro-angiogenic cells to the microenvironment. We are testing this hypothesis in a robust xenograft model. These experiments will establish if IL-8 plays a role in progression and metastasis of canine HSA, and allow us to define the therapeutic potential of IL-8 blockade.