Purchase this article with an account.
Vanessa Marie Morales, Zachary K. Goldsmith, Neel Patel, Benjamin A King, Hans E Grossniklaus, Matthew W Wilson; Microenvironmental Regulation of the Liver Inflammasomes in Uveal Melanoma Favors Metastatic Growth. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3959. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Many challenges remain in our understanding of the development of metastasis. Uveal melanoma disseminates hematogenously to the liver. The events in the microenvironment leading to immune cell activation for tumor clearance are not fully understood. The recently described inflammasomes are signaling scaffolds that trigger innate immune activation promoting pyroptosis, a recently described type of programmed cell death by activation of caspase-1. In this study we investigated the presence of inflammasomes in the metastatic liver in an orthotopic xenograft uveal melanoma animal model and a patient post mortem.
We received approval for the Institutional Review Board at the University of Tennessee Health Science Center to perform analyses on post mortem tissue of uveal melanoma patients and compared them to healthy livers. Liver samples of an orthotopic xenograft model were also examined. We performed Western blot analyses on 4-described inflammasomes: NLRP1, NLRP2, NLRP3, and NLRP12, in addition to caspase-1 analysis.
Western blot results show absence of most known inflammasomes in the metastatic uveal melanoma liver compared to healthy liver. Multiple areas of the metastatic liver were examined and found similar results. We investigated expression of caspase-1 in these samples and found presence only in healthy liver samples.
Our work suggests the liver inflammasommes may contribute to clearance of metastasis in the liver. Further work is needed to understand the components of the liver inflammasomes and define factors, which may serve as drug targets to reduce metastasis.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only