Anti-CEBPB monoclonal antibody

The placenta is the principal organ regulating respiratory, nutritional, endocrine and metabolic functions on behalf of the developing fetus. Changes in gene expression patterns of placenta-specific genes may influence fetal growth. We profiled the expression of 17 genes related to placenta functioning in term placentas (n = 677) to identify genes differentially expressed across birth weight categories [ small (SGA), appropriate (AGA) and large (LGA) for gestational age]. ABCG2, CEBPB, CRH, GCM1, GPC3, INSL4, PGF and PLAC1 were inversely associated with LGA status, with odds ratios (ORs) and 95% confidence intervals (CI) ranging from GCM1 (OR = 0.44, 95% CI: 0.29, 0.70) to CRH (OR = 0.73, 95% CI: 0.61, 0.88). NR3C1 was positively associated with LGA status (OR = 2.33, 95% CI: 1.43, 3.78). PLAC1 (OR = 0.66, 95% CI: 0.47, 0.92) and ABCG2 (OR = 0.63, 95% CI: 0.44, 0.91) were additionally inversely associated with SGA status, and PGF was positively associated with SGA status (OR = 1.59, 95% CI = 1.08, 2.35). General trends were confirmed in an independent cohort (n = 306). Given that aberrant fetal growth may have long-lasting effects, our results suggest the potential utility of placental gene expression profiles as potential early markers of disease onset later in life.

Catabolism of the essential amino acid tryptophan is a key metabolic pathway contributing to the immunosuppressive tumor microenvironment and therefore a viable drug target for cancer immunotherapy. In addition to the rate-limiting enzyme indoleamine-2,3-dioxygenase-1 (IDO1), tryptophan catabolism via tryptophan-2,3-dioxygenase (TDO2) is a feature of many tumors, particularly malignant gliomas. The pathways regulating TDO2 in tumors are poorly understood; using unbiased promoter and gene expression analyses, we identify a distinct CCAAT/enhancer-binding protein beta (C/EBP beta) binding site in the promoter of TDO2 essential for driving constitutive TDO2 expression in glioblastoma cells. Using The Cancer Genome Atlas (TCGA) data, we find that C/EBP beta expression is correlated with TDO2, and both are enriched in malignant glioma of the mesenchymal subtype and associated with poor patient outcome. We determine that TDO2 expression is sustained mainly by the LAP isoform of CEBPB and interleukin-1 beta, which activates TDO2 via C/EBP beta in a mitogen-activated protein kinase (MAPK) kinase-dependent fashion. In summary, we provide evidence for a novel regulatory and therapeutically targetable pathway of immunosuppressive tryptophan degradation in a subtype of glioblastoma with a particularly poor prognosis.