Dataset Information

Elevated plasma levels of the pituitary hormone Cthrc1 in individuals with red hair but not in patients with solid tumors.

ABSTRACT:

Background

An increasing number of studies report that Cthrc1 is expressed in various cancer cells. The present study sought to identify which cells in tumors and remodeling tissues express Cthrc1 and investigate the range of circulating human Cthrc1 levels in health and disease.

Methodology/principle findings

Highly specific monoclonal antibodies were generated to detect Cthrc1 by ELISA in plasma and in tissues by immunohistochemistry. In human colon, gastric, breast, endometrial, pancreatic, kidney, lung and skin cancer, Cthrc1 was expressed by activated stromal cells and not the cancer cells themselves. Similarly, conditions evoking tissue remodeling, such as wound repair or angiotensin II-mediated hypertension, induced Cthrc1 expression in interstitial and adventitial fibroblasts and perivascular stromal cells. Levels of Cthrc1 in plasma from healthy subjects were near the lower detection limit except for individuals with red hair, who had up to several hundred fold higher levels. Elevated Cthrc1 was also found in patients with diabetes, inflammatory conditions, and infections, but not solid tumors. Transgenic mouse studies suggested that Cthrc1 expression by stromal cells does not contribute to circulating levels. In human pituitaries, Cthrc1 was expressed in the anterior and intermediate lobes with unencapsulated Cthrc1 accumulations typically surrounded by chromophobe cells.

Conclusions

We identify Cthrc1 as a marker for activated stromal cells. Cthrc1 is a pituitary hormone with significantly elevated levels in subjects carrying variant alleles of the melanocortin-1 receptor as wells as in patients with inflammatory conditions.

SUBMITTER: Duarte CW

PROVIDER: S-EPMC4063940 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Elevated plasma levels of the pituitary hormone Cthrc1 in individuals with red hair but not in patients with solid tumors.

Duarte Christine W CW Stohn J Patrizia JP Wang Qiaozeng Q Emery Ivette F IF Prueser Andrew A Lindner Volkhard V

PloS one 20140619 6

<h4>Background</h4>An increasing number of studies report that Cthrc1 is expressed in various cancer cells. The present study sought to identify which cells in tumors and remodeling tissues express Cthrc1 and investigate the range of circulating human Cthrc1 levels in health and disease.<h4>Methodology/principle findings</h4>Highly specific monoclonal antibodies were generated to detect Cthrc1 by ELISA in plasma and in tissues by immunohistochemistry. In human colon, gastric, breast, endometrial ...[more]

PMID: 24945147

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Project description:BackgroundCirculating plasma miRNAs have been increasingly studied in the field of pituitary neuroendocrine tumor (PitNET) research. Our aim was to discover circulating plasma miRNAs species associated with growth hormone (GH) secreting PitNETs versus assess how the plasma levels of discovered miRNA candidates are impacted by SSA therapy and whether there is a difference in their levels between GH secreting PitNETs versus other PitNET types and healthy individuals.DesignWe compared plasma miRNA content and levels before and after surgery focusing on GH secreting PitNET patients. Selected miRNA candidates from our data and literature were then tested in a longitudinal manner in somatostatin analogues (SSA) treatment group. Additionally, we validated selected targets in an independent GH secreting PitNET group.MethodsmiRNA candidates were discovered using the whole miRNA sequencing approach and differential expression analysis. Selected miRNAs were then analyzed using real-time polymerase chain reaction (qPCR).ResultsWhole miRNA sequencing discovered a total of 16 differentially expressed miRNAs (DEMs) in GH secreting PitNET patients' plasma 24 hours after surgery and 19 DEMs between GH secreting PitNET patients' plasma and non-functioning (NF) PitNET patients' plasma. Seven miRNAs were selected for further testing of which miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p showed a significant downregulation in plasma after 1 month of SSA treatment. mir-625-5p was found to be significantly downregulated in plasma of GH secreting PitNET patients vs. NF PitNET patients. miR-625-5p alongside miR-130b-3p were also found to be downregulated in GH PitNETs compared to healthy individuals.ConclusionsOur study suggests that expression of plasma miRNAs miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p in GH secreting PitNETs is affected by SSA treatment. Additionally, miR-625-5p can distinguish GH secreting PitNETs from other PitNET types and healthy controls warranting further research on these miRNAs for treatment efficacy.

Project description:Background and aimAbout a third of Pituitary Neuroendocrine Tumors (PitNETs) may show aggressive behavior. Many efforts have been performed for identifying possible predictive factors to early determine the future behavior of PitNETs. Programmed cell death ligand 1 (PD-L1) expression was associated with a more aggressive biology in different solid tumors, but its role in PitNET is not well-established yet. Our study aims to analyze PD-L1 expression in a surgical cohort of PitNETs to determine its association with radiological invasion and pathology findings, as well as with long-term recurrence rates.MethodsWe performed a retrospective analysis in a series of 86 PitNETs. Clinical presentation and radiological features of the preoperative period were collected, as well as pathological data and follow-up data. The rate of PD-L1 expression was immunohistochemically evaluated and expressed as a tumor proportion score (TPS). We assessed its relationship with cavernous sinus invasion and Trouillas' classification as primary outcomes. Secondary outcomes included the TPS' relationship with histopathological markers of proliferation, hormonal expression, tumor size and long-term recurrence rates. We calculated the optimal cut-point for the primary outcomes while maximizing the product of the sensitivity and specificity and then we evaluated the significance of secondary outcomes with logistic regression analysis.ResultsEighty-six patients were included in the analysis; 50 cases were non-functional PitNETs. The TPS for PD-L1 showed a highly right-skewed distribution in our sample, as 30.2% of patients scored 0. Using Trouillas' classification, we found that "proliferative" cases have a significantly higher probability to express PD-L1 in more than 30% of tumor cells (OR: 5.78; CI 95%: 1.80-18.4). This same cut-point was also associated with p53 expression. A positive association was found between PD-L1 expression and GH expression (p = 0.001; OR: 5.44; CI 95%: 1.98-14.98), while an inverse relationship was found with FSH/LH expression (p = 0.014; OR = 0.27, CI 95%: 0.10-0.76). No association was found with CS invasion, tumor size, bone erosion or dura invasion. We could not find any association between PD-L1 expression and recurrence.ConclusionsPD-L1 expression was associated with proliferative grades of Trouillas' classification and p53 expression. We also confirmed a higher expression of PD-L1 in somatotroph tumors. Larger studies are necessary to investigate the relationship between PD-L1 expression and aggressive behaviors.

Dataset Information

Elevated plasma levels of the pituitary hormone Cthrc1 in individuals with red hair but not in patients with solid tumors.

Background

Methodology/principle findings

Conclusions

Publications

Elevated plasma levels of the pituitary hormone Cthrc1 in individuals with red hair but not in patients with solid tumors.

Similar Datasets

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