Many cancer cells, regardless of their tissue origin or genetic landscape, have increased expression or activity of the plasma membrane Na-H exchanger NHE1 and a higher intracellular pH (pHi) compared with untransformed cells. A current perspective that remains to be validated is that increased NHE1 activity and pHi enable a Warburg-like metabolic reprogramming of increased glycolysis and decreased mitochondrial oxidative phosphorylation. We tested this perspective and find it is not accurate for clonal pancreatic and breast cancer cells.
View Article and Find Full Text PDFMitochondria control eukaryotic cell fate by producing the energy needed to support life and the signals required to execute programed cell death. The biochemical milieu is known to affect mitochondrial function and contribute to the dysfunctional mitochondrial phenotypes implicated in cancer and the morbidities of aging. However, the physical characteristics of the extracellular matrix are also altered in cancerous and aging tissues.
View Article and Find Full Text PDFCell migration exerts a pivotal role in tumor progression, underlying cell invasion and metastatic spread. The cell migratory program requires f-actin re-organization, generally coordinated with the assembly of focal adhesions. Ion channels are emerging actors in regulating cell migration, through different mechanisms.
View Article and Find Full Text PDFThe integration of microfluidics and cell biology has reached a significant milestone with the development of "organ-on-chips", smart technological platforms that, once applied to the study of human diseases, such as cancer, might ultimately contribute to design personalised treatments and hence improve health outcomes. This paper reports that the combination of microfluidics and dielectrophoresis (DEP) allows to culture different pancreatic ductal adenocarcinoma (PDAC) human cell lines into a cyclic olefin polymer (COP) chamber (HepaChip), enriched by the extracellular matrix (ECM) protein collagen. We show that PDAC cells cultured into the HepaChip (1) are vital and grow, provided they properly attach to collagen; (2) show morphological appearance and growth characteristics closer to those of cells grown as spheroids than as classical 2 dimensional (2D) in vitro cultures.
View Article and Find Full Text PDFIon channels regulate cell proliferation, differentiation, and migration in normal and neoplastic cells through cell-cell and cell-extracellular matrix (ECM) transmembrane receptors called integrins. K flux through the human ether-à-go-go-related gene 1 (hERG1) channel shapes action potential firing in excitable cells such as cardiomyocytes. Its abundance is often aberrantly high in tumors, where it modulates integrin-mediated signaling.
View Article and Find Full Text PDFThe success of gene therapy depends on safe and effective gene carriers. Despite being widely used, synthetic vectors based on poly(ethylenimine) (PEI), poly(l-lysine) (PLL), or poly(l-arginine) (poly-Arg) are not yet fully satisfactory. Thus, both improvement of established carriers and creation of new synthetic vectors are necessary.
View Article and Find Full Text PDFTransient gene expression (TGE) is a rapid method for the production of recombinant proteins in mammalian cells. While the TGE volumetric productivity has improved significantly over the past decade, the amount of plasmid DNA (pDNA) needed for transfection remains very high. Here, we examined the use of non-specific (filler) DNA to partially replace the transgene-bearing plasmid DNA (coding pDNA) in transfections of Chinese hamster ovary (CHO) and human embryo kidney (HEK-293E) cells.
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