Anti-CTBP1 monoclonal antibody, clone FQS7911

The neuropeptide growth hormone-releasing hormone (GHRH) is secreted by the hypothalamus and upon the binding to the receptors for GHRH on the pituitary gland regulates the release of growth hormone Substantial evidence indicate that GHRH. in addition to its physiological role as a hypophysiotrophic hormone. acts as a growth factor in diverse tissues and various tumors In this study we evaluated the expression of GHRH and its receptors in a variety of cancel and non-cancerous cell lines and studied the effect of GHRH antagonists and agonists on the proliferative cell nuclear antigen. cyclin D3, tumor suppressor protein p53 and carboxyl-terminal-binding protein (CtBP1) Our findings show that GHRH agonist JI-38 downregulates wt-p53 and upregulates the expression of PCNA GHRH also upregulates CtBP1 protein expression and its antagonists downregulate it in LNCaP prostate cancer cells Furthermore. GHRH and its agonist JI-38 upregulates the expression of the proliferative markers cyclin D3 and PCNA in A549 non-small cell lung carcinoma and GHRH antagonist MZ-5-156 downregulates it Our results support previous findings on the mitogenic role of GHRH in cancers and underline the importance of GHRH antagonists as anticancer agents

About 20% of prostate cancer (PCa) patients progress to metastatic disease. Metabolic syndrome (MeS) is a pathophysiological disorder that increases PCa risk and aggressiveness. C-terminal binding protein (CTBP1) is a transcriptional corepressor that is activated by high-fat diet (HFD). Previously, our group established a MeS/PCa mice model that identified CTBP1 as a novel link associating both diseases. Here, we integrated in vitro (prostate tumor cell lines) and in vivo (MeS/PCa NSG mice) models with molecular and cell biology techniques to investigate MeS/CTBP1 impact over PCa progression, particularly over cell adhesion, mRNA/miRNA expression and PCa spontaneous metastasis development. We found that CTBP1/MeS regulated expression of genes relevant to cell adhesion and PCa progression, such as cadherins, integrins, connexins, and miRNAs in PC3 xenografts. CTBP1 diminished PCa cell adhesion, membrane attachment to substrate and increased filopodia number by modulating gene expression to favor a mesenchymal phenotype. NSG mice fed with HFD and inoculated with CTBP1-depleted PC3 cells, showed a decreased number and size of lung metastases compared to control. Finally, CTBP1 and HFD reduce hsa-mir-30b-5p plasma levels in mice. This study uncovers for the first time the role of CTBP1/MeS in PCa progression and its molecular targets.