Cross-talk between the tumor microenvironment, extracellular matrix, and cell metabolism in cancer

The extracellular matrix (ECM) is a complex network of secreted proteins which provides support for tissues and organs. Additionally, the ECM controls a plethora of cell functions, including cell polarity, migration, proliferation, and oncogenic transformation. One of the hallmarks of cancer is altered cell metabolism, which is currently being exploited to develop anti-cancer therapies. Several pieces of evidence indicate that the tumor microenvironment and the ECM impinge on tumor cell metabolism. Therefore, it is essential to understand the contribution of the complex 3D microenvironment in controlling metabolic plasticity and responsiveness to therapies targeting cell metabolism. In this mini-review, we will describe how the tumor microenvironment and cancer-associated fibroblasts dictate cancer cell metabolism, resulting in increased tumor progression. Moreover, we will define the cross-talk between nutrient signaling and the trafficking of the ECM receptors of the integrin family. Finally, we will present recent data highlighting the contribution of nutrient scavenging from the microenvironment to support cancer cells growth under nutrient starvation conditions

Analysis of the DNA methylation pattern of the promoter region of calcitonin gene-related peptide 1 gene in patients with episodic migraine: An exploratory case-control study

Recent studies suggested that epigenetic mechanisms, including DNA methylation, may be involved in migraine pathogenesis. The calcitonin gene-related peptide (CGRP), encoded by calcitonin gene-related peptide 1 (CALCA) gene, plays a key role in the disease. The aim of the study was to evaluate DNA methylation of CALCA gene in patients with episodic migraine. 22 patients with episodic migraine (F/M 15/7, mean age 39.7 ± 13.4 years) and 20 controls (F/M 12/8, mean age 40.5 ± 14.8 years) were recruited. Genomic DNA was extracted from peripheral blood. Cytosine-to-thymine conversion was obtained with sodium bisulfite. The methylation pattern of two CpG islands in the promoter region of CALCA gene was analyzed. No difference of methylation of the 30 CpG sites at the distal region of CALCA promoter was observed between migraineurs and controls. Interestingly, in patients with episodic migraine the methylation level was lower in 2 CpG sites at the proximal promoter region (CpG −1461, p = 0.037, and −1415, p = 0.035, respectively). Furthermore, DNA methylation level at different CpG sites correlates with several clinical characteristics of the disease, as age at onset, presence of nausea/vomiting, depression and anxiety (p < 0.05). In conclusion, we found that DNA methylation profile in two CpG sites at the proximal promoter region of CALCA is lower in migraineurs when compared to controls. Intriguingly, the −1415 hypomethylated unit is located at the CREB binding site, a nuclear transcription factor. In addition, we found a correlation between the level of CALCA methylation and several clinical features of migraine. Further studies with larger sample size are needed to confirm these results

Increased orexin A concentrations in cerebrospinal fluid of patients with behavioural variant frontotemporal dementia

Orexins are hypothalamic neuropeptides that regulate several physiological functions, such as appetite, arousal, cognition, stress, sleep and metabolism. Emerging pieces of evidence suggest an orexinergic dysfunction in several neuropsychiatric disorders, including depression, anxiety and addiction. A syndromic overlap between behavioural variant frontotemporal dementia (bvFTD) and several psychiatric disorders was recently demonstrated. Therefore, we analysed cerebrospinal fluid (CSF) orexin A concentrations of 40 bvFTD and 32 non-demented patients, correlating neuropeptide concentrations with several clinical characteristics. A significant increase of orexin A concentrations was found in bvFTD patients when compared to controls (p<0.001). CSF orexin A concentration showed a correlation with Mini-Mental State Examination scores, drug assumption, history of compulsive behaviour and extrapyramidal signs. Moreover, we found a relationship between CSF markers of neurodegeneration, total tau and Aβ(1–42) and CSF orexin A concentrations. Our study provides evidence of an orexinergic dysfunction in bvFTD, correlating with several clinical symptoms. Further larger studies are needed to confirm our data. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-021-05250-x