LAUSR

Introduction Metastasis is the primary cause of death in cancer patients. The implantation and growth of metastatic cells in secondary organs is dependent on both cell-intrinsic factors and microenvironmental (‘host’) factors. Host cells are activated in response to oncogenic signals to acquire pro- or anti-tumoral properties, but the mechanisms of translational control that regulate this process remain largely unknown. Here, we study the role of the RNA-binding protein Cytoplasmic Polyadenylation Element Binding Protein 4 (CPEB4) in the metastatic niche. CPEB4 regulates temporally and spatially the translation efficiency and stability of up to 30% of mammalian mRNAs, and has been shown to regulate the expression of inflammation and angiogenesis-related genes such as VEGFA and IL6 in non-tumoral contexts. Material and methods The metastatic melanoma cell line B16F10 was used in an experimental metastasis assay to determine the contribution of host CPEB4 to metastatic growth. Syngenic wild type (WT) and CPEB4 full knock-out (KO) animals were tail-vein injected with B16F10 and lung metastasis number and size were quantified. Immune cell infiltration in untreated or tumor-bearing WT and KO was measured by FACS and IHC. Results and discussions Depletion of host CPEB4 resulted in an increased lung metastasis size and a higher frequency of extrapulmonary metastasis. In contrast, primary tumour growth was comparable between WT and KO animals, suggesting that stromal CPEB4 has a prevailing role in secondary organs compared to B16F10 primary tumour niche. In addition, immunophenotyping analysis of metastatic organs revealed alterations in the immune cell composition of CPEB4 KO lungs. Conclusion Our preliminary results suggest that host CPEB4 is required to restrain metastatic growth. We hypothesised that lacking CPEB4 favours a more pro-metastatic environment due to changes in the immune cell compartment of the metastatic niche. Our future experiments will address whether CPEB4 depletion impairs directly immune cell function in a cell autonomous manner or whether other lung microenvironment cell types mediate the observed alterations.