| 11. |
- Gonzalez-Molina, J, et al.
(författare)
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The extracellular fluid macromolecular composition differentially affects cell-substrate adhesion and cell morphology
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 8505-
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Tidskriftsartikel (refereegranskat)abstract
- Soluble macromolecules present in the tumour microenvironment (TME) alter the physical characteristics of the extracellular fluid and can affect cancer cell behaviour. A fundamental step in cancer progression is the formation of a new vascular network which may originate from both pre-existing normal endothelium and cancer-derived cells. To study the role of extracellular macromolecules in the TME affecting endothelial cells we exposed normal and cancer-derived endothelial cells to inert polymer solutions with different physicochemical characteristics. The cancer cell line SK-HEP-1, but not normal human umbilical vein endothelial cells, responded to high-macromolecular-content solutions by elongating and aligning with other cells, an effect that was molecular weight-dependent. Moreover, we found that neither bulk viscosity, osmotic pressure, nor the fractional volume occupancy of polymers alone account for the induction of these effects. Furthermore, these morphological changes were accompanied by an increased extracellular matrix deposition. Conversely, cell-substrate adhesion was enhanced by polymers increasing the bulk viscosity of the culture medium independently of polymer molecular weight. These results show that the complex macromolecular composition of the extracellular fluid strongly influences cancer-derived endothelial cell behaviour, which may be crucial to understanding the role of the TME in cancer progression.
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| 12. |
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| 13. |
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| 14. |
- Rodriguez-Cortez, VC, et al.
(författare)
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Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition
- 2015
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 7335-
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Tidskriftsartikel (refereegranskat)abstract
- Common variable immunodeficiency (CVID), the most frequent primary immunodeficiency characterized by loss of B-cell function, depends partly on genetic defects, and epigenetic changes are thought to contribute to its aetiology. Here we perform a high-throughput DNA methylation analysis of this disorder using a pair of CVID-discordant MZ twins and show predominant gain of DNA methylation in CVID B cells with respect to those from the healthy sibling in critical B lymphocyte genes, such as PIK3CD, BCL2L1, RPS6KB2, TCF3 and KCNN4. Individual analysis confirms hypermethylation of these genes. Analysis in naive, unswitched and switched memory B cells in a CVID patient cohort shows impaired ability to demethylate and upregulate these genes in transitioning from naive to memory cells in CVID. Our results not only indicate a role for epigenetic alterations in CVID but also identify relevant DNA methylation changes in B cells that could explain the clinical manifestations of CVID individuals.
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