leptin and Meningioma

Recent increase in incidence of meningiomas suggests the need to search for new risk factors. Leptin, a potentially pro-angiogenic and proliferative agent, could be a candidate for this role, as its expression correlates with body mass index (BMI). Because development of meningioma has also been linked to sex hormones, bisphenol A (BPA), a known xenoestrogen, can also be taken into consideration as a potential risk factor. The aim of this study was to determine plasma concentrations of both substances in patients with meningiomas and to match it to patients with gliomas - a group of brain tumors less hormone- and BMI-dependent.. Concentrations of BPA and leptin were measured in plasma of 24 patients with low grade meningioma and in 29 patients with glioma, using gas chromatography-mass spectrometry (GC-MS) and ELISA kits, respectively. The concentrations of both substances in patients with neoplasms were interpreted in relation to their concentration in healthy population, published in recent reports.. Free and conjugated BPA were present in both meningioma and glioma patients. Moreover, their concentrations far exceeded those reported in the healthy population. Nevertheless, the level of leptin revealed to be significantly higher in meningioma patients than in glioma patients.. Occurrence of both meningioma and glioma may be accompanied by increased concentrations of leptin and BPA. Further large-scale studies are needed to clarify whether the presence of both substances may play a role in pathogenesis or influence clinical course in patients with brain neoplasms.

Topics: Brain Neoplasms; Glioma; Gonadal Steroid Hormones; Humans; Leptin; Meningeal Neoplasms; Meningioma; Pilot Projects

Tumor cells recapitulate cell-lineage transcriptional programs that are characteristic of normal tissues from which they arise. It is unclear why such lineage programs are fatefully maintained in tumors and if they contribute to cell proliferation and viability.. Here, we used the most common brain tumor, meningioma, which is strongly associated with female sex and high body mass index (BMI), as a model system to address these questions. We screened expression profiling data to identify the transcription factor (TF) genes which are highly enriched in meningioma, and characterized the expression pattern of those TFs and downstream genes in clinical meningioma samples as well as normal brain tissues. Meningioma patient-derived cell lines (PDCLs) were used for further validation and characterization.. We identified 8 TFs highly enriched in meningioma. Expression of these TFs, which included sine oculis homeobox 1 (SIX1), readily distinguished meningiomas from other primary brain tumors and was maintained in PDCLs and even in pulmonary meningothelial nodules. In meningioma PDCLs, SIX1 and its coactivator eyes absent 2 (EYA2) supported the expression of the leptin receptor (LEPR), the cell-surface receptor for leptin (LEP), the adipose-specific hormone that is high in women and in individuals with high BMI. Notably, these transcriptional regulatory factors, LEPR and LEP, both contributed to support meningioma PDCLs proliferation and survival, elucidating a survival dependency on both a core transcriptional program and a metabolic cell-surface receptor.. These findings provide one rationale for why lineage TF expression is maintained in meningioma and for the epidemiological association of female sex and obesity with meningioma risk.

Topics: Animals; Apoptosis; Biomarkers, Tumor; Case-Control Studies; Cell Cycle; Cell Lineage; Cell Proliferation; Cohort Studies; Female; Follow-Up Studies; Homeodomain Proteins; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Male; Meningeal Neoplasms; Meningioma; Mice; Middle Aged; Nuclear Proteins; Obesity; Prognosis; Protein Tyrosine Phosphatases; Receptors, Immunologic; Receptors, Leptin; Receptors, Prostaglandin; Survival Rate; Tissue Array Analysis; Transcription Factors; Tumor Cells, Cultured; Xenograft Model Antitumor Assays