Social status hierarchies are ubiquitous in vertebrate social systems, including humans. It is well known that social rank can influence quality of life dramatically among members of social groups. For example, high-ranking individuals have greater access to resources, including food and mating prerogatives that, in turn, have a positive impact on their reproductive success and health. In contrast low ranking individuals typically have limited reproductive success and may experience lasting social and physiological costs. Ultimately, social rank and behavior are regulated by changes in gene expression. However, little is known about mechanisms that transduce social cues into transcriptional changes. Since social behavior is a dynamic process, we hypothesized that a molecular mechanism such as DNA methylation might play a role these changes. To test this hypothesis, we used an African cichlid fish, Astatotilapia burtoni, in which social rank dictates reproductive access. We show that manipulating global DNA methylation state strongly biases the outcomes of social encounters. Injecting DNA methylating and de-methylating agents in low status animals competing for status, we found that animals with chemically increased methylation states were statistically highly likely to ascend in rank. In contrast, those with inhibited methylation processes and thus lower methylation levels were statistically highly unlikely to ascend in rank. This suggests that among its many roles, DNA methylation may be linked to social status and more generally to social behavior.

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In several cancers, tumor progression is associated with the infiltration of tumor-associated macrophages (TAMs). The aim was to evaluate the prognostic significance of expression of CD163 and CD68 (TAMs’ markers) and their correlation with vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) expression in cutaneous melanoma. Diagnostic tissues from 102 patients of cutaneous melanoma were evaluated by immunohistochemistry for their CD68, CD163, VEGF, and COX-2 expression. Correlations between the proteins were then investigated. Clinicopathological features, overall survival (OS), and progression-free survival were analyzed in terms of the expression of these proteins. CD163, but not CD68, expression correlated with VEGF and COX-2 expression. High expression for CD163 was associated with a deeper Breslow thickness and an advanced stage of the disease. High expression of CD163 was associated with lower OS. No significant differences were noted in CD68 expression between the clinicopathological variables and the OS. COX-2 expression was associated with a deeper Breslow thickness and a higher frequency of lymph node involvement. Multivariate analysis revealed that CD163 expression and COX-2 expression were independent prognostic markers of lower survival outcomes. Our data confirmed that CD163 expression provides independent prognostic information in cutaneous melanoma. The correlation of CD163 with VEGF and COX-2 expression suggests various tumor-promoting actions of CD163-positive TAMs.

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