Biology subjects

Peres, J.

Publications and source records attributed to Peres, J..

3 recordsLinked to original sources

bioRxiv2026

Physiological caffeine concentrations do not affect enteric neural crest cell migration in a mouse model

The defect in enteric neural crest cell (ENCCs) migration that causes Hirschsprung disease (HD) in newborns is linked to genetic and likely also environmental factors. Among these, maternal coffee consumption has been associated with increased HD risk, yet the role of caffeine on ENCC migration has remained unexplored. Here, we show that although mouse ENCCs express caffeine-sensitive ADORA2A receptors, physiological doses of caffeine do not perturb endogenous ENCC calcium activity. We find that caffeine can modulate ENCC outgrowth in a 2D culture model but that it does not affect migration in a 3D collagen gel and in the ex-vivo embryonic gut. We conclude that physiological doses of caffeine do not hamper ENCC migration in the ex-vivo embryonic mouse intestine, thereby discarding a potential direct environmental mechanism of caffeine in HD.

developmental biology↗

bioRxiv2022

Intracellular mechanics and TBX3 expression jointly dictate the spreading mode of melanoma cells in 3D environments

Cell stiffness and T-box transcription factor 3 (TBX3) expression have been identified as biomarkers of melanoma metastasis in 2D environments. This study aimed to determine how mechanical and biochemical properties of melanoma cells change during cluster formation in 3D environments. Vertical growth phase (VGP) and metastatic (MET) melanoma cells were embedded in 3D collagen matrices of 2 and 4 mg/ml collagen concentrations, representing low and high matrix stiffness. Mitochondrial fluctuation, intracellular stiffness, and TBX3 expression were quantified before and during cluster formation. In isolated cells, mitochondrial fluctuation decreased and intracellular stiffness increased with increase in disease stage from VGP to MET and increased matrix stiffness. TBX3 was highly expressed in soft matrices but diminished in stiff matrices for VGP and MET cells. Cluster formation of VGP cells was excessive in soft matrices but limited in stiff matrices, whereas for MET cells it was limited in soft and stiff matrices. In soft matrices, VGP cells did not change the intracellular properties, whereas MET cells exhibited increased mitochondrial fluctuation and decreased TBX3 expression. In stiff matrices, mitochondrial fluctuation and TBX3 expression increased in VGP and MET, and intracellular stiffness increased in VGP but decreased in MET cells. The findings suggest that soft extracellular environments are more favourable for tumour growth, and high TBX3 levels mediate collective cell migration and tumour growth in the earlier VGP disease stage but play a lesser role in the later metastatic stage of melanoma. Symbols O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=184 SRC="FIGDIR/small/495509v4_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1444cf4org.highwire.dtl.DTLVardef@118427eorg.highwire.dtl.DTLVardef@1b56a0aorg.highwire.dtl.DTLVardef@144d41f_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2020

Cytoskeletal Tubulin Competes with Actin to Increase Deformability of Metastatic Melanoma Cells

The formation of membrane protrusions during migration is reliant upon the cells cytoskeletal structure and stiffness. It has been reported that actin disruption blocks protrusions and decreases cell stiffness whereas microtubule disruption blocks protrusion but increases stiffness in several cell types. In melanoma, cell migration is of concern as this cancer spreads unusually rapidly during early tumour development. The aim of this study was to characterise motility, structural properties and stiffness of human melanoma cells at radial growth phase (RGP), vertical growth phase (VGP), and metastatic stage (MET) in two-dimensional in vitro environments. Wound assays, western blotting and mitochondrial particle tracking were used to assess cell migration, cytoskeletal content and intracellular fluidity. Our results indicate that cell motility increase with increasing disease stage. Despite their different motility, RGP and VGP cells exhibit similar fluidity, actin and tubulin levels. MET cells, however, display increased fluidity which was associated with increased actin and tubulin content. Our findings demonstrate an interplay between actin and microtubule activity and their role in increasing motility of cells while minimizing cell stiffness at advanced disease stage. In earlier disease stages, cell stiffness may however not serve as an indicator of migratory capabilities.

cancer biology↗