High extracellular S100A4 level proves a specific characteristic of some cancer cases, including malignant melanoma. Concerning the latter, extracellular S100A4 in an autocrine manner was shown to promote prometastatic activation of A375 cells by interaction with the receptor for advanced glycation endproducts (RAGE). We hypothesized that interaction of extracellular S100A4 with RAGE in a paracrine manner will affect endothelial cell (EC) integrity thus further promoting melanoma metastasis. We investigated the influence of recombinant and cell (A375)-derived S100A4 on junction protein expression and EC (hCMEC/D3) integrity by measuring transendothelial electrical resistance (TEER). Decrease of TEER and diminished expression of both occludin and VE-cadherin revealed the loss of EC integrity. Transmigration of transgenic A375 cells (A375-hS100A4/A375-hRAGE) through the EC monolayer was significantly higher compared to wild-type A375 cells, and was substantially decreased by sRAGE. A pilot study in mice, intracardially injected with A375-hS100A4 or A375-hRAGE cells, showed lower survival rates and a higher incidence of metastases compared to wild-type A375 cells. Tumor development was mostly located in the brain, bones, and ovaries. These findings provide further evidence on extracellular S100A4 as paracrine mediator of prometastatic endothelial dysfunction involving its interaction with RAGE.
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http://dx.doi.org/10.1016/j.bbrc.2016.07.009 | DOI Listing |
Mil Med Res
December 2024
Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China.
Background: With the increasing risk of nuclear exposure, more attention has been paid to the prevention and treatment of acute radiation syndrome (ARS). Although amino acids are key nutrients involved in hematopoietic regulation, the impacts of amino acids on bone marrow hematopoiesis following irradiation and the associated mechanisms have not been fully elucidated. Hence, it is of paramount importance to study the changes in amino acid metabolism after irradiation and their effects on hematopoiesis as well as the related mechanisms.
View Article and Find Full Text PDFJ Tissue Eng
November 2024
Institute for Computational Systems Biology, University of Hamburg, Hamburg, Germany.
Non-healing bone defects are a pressing public health concern accounting for one main cause for decreased life expectancy and quality. An aging population accompanied with increasing incidence of comorbidities, foreshadows a worsening of this socio-economic problem. Conventional treatments for non-healing bone defects prove ineffective for 5%-10% of fractures.
View Article and Find Full Text PDFSci Rep
July 2024
Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Science, Linköping University, 581 83, Linköping, Sweden.
Inflammation, corticosteroids, and loading all affect tendon healing, with an interaction between them. However, underlying mechanisms behind the effect of corticosteroids and the interaction with loading remain unclear. The aim of this study was to investigate the role of dexamethasone during tendon healing, including specific effects on tendon cells.
View Article and Find Full Text PDFBiochem Biophys Res Commun
October 2024
Insitute for Molecular Science of Medicine, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan. Electronic address:
Versican is a large chondroitin sulfate proteoglycan in the extracellular matrix. It plays a pivotal role in the formation of the provisional matrix. S100a4, previously known as fibroblast-specific protein, functions as a calcium channel-binding protein.
View Article and Find Full Text PDFJ Biol Chem
June 2024
Department of Biochemistry, ELTE Eötvös Loránd University, Budapest, Hungary. Electronic address:
Non-muscle myosin 2 (NM2) is known to play an important role in myofibroblast transdifferentiation, a hallmark of fibrotic disorders. In a recent JBC article, Southern et al. demonstrate that endogenous S100A4, a calcium- and NM2-binding protein acts as a mechanoeffector in this process.
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