Vol 9: Knock-Down of CD44 Regulates Endothelial Cell Differentiation via NFB-Mediated Chemokine Production.Report as inadecuate



 Vol 9: Knock-Down of CD44 Regulates Endothelial Cell Differentiation via NFB-Mediated Chemokine Production.


Vol 9: Knock-Down of CD44 Regulates Endothelial Cell Differentiation via NFB-Mediated Chemokine Production. - Download this document for free, or read online. Document in PDF available to download.

Download or read this book online for free in PDF: Vol 9: Knock-Down of CD44 Regulates Endothelial Cell Differentiation via NFB-Mediated Chemokine Production.
This article is from PLoS ONE, volume 9.AbstractA striking feature of microvascular endothelial cells is their capacity to fuse and differentiate into tubular structures when grown in three-dimensional 3D extracellular matrices, in collagen or Matrigel, mimicking the in vivo blood vessel formation. In this study we demonstrate that human telomerase-immortalised foreskin microvascular endothelial TIME cells express high levels of the hyaluronan receptor CD44 and the hyaluronidase HYAL2. Knock-down of CD44 or HYAL2 resulted in an inability of TIME cells to form a tubular network, suggesting a key regulatory role of hyaluronan in controlling TIME cell tubulogenesis in 3D matrices. Knock-down of CD44 resulted in an upregulation of mRNA expression of the chemokines CXCL9 and CXCL12, as well as their receptors CXCR3 and CXCR4. This was accompanied by a defect maturation of the tubular structure network and increased phosphorylation of the inhibitor of NFκB kinase IKK complex and thus translocation of NFκB into the nucleus and activation of chemokine targed genes. Furthermore, the interaction between CD44 and hyaluronan determines the adhesion of breast cancer cells. In summary, our observations support the notion that the interaction between CD44 and hyaluronan regulates microvascular endothelial cell tubulogenesis by affecting the expression of cytokines and their receptors, as well as breast cancer dissemination.



Author: Olofsson, Berit; Porsch, Helena; Heldin, Paraskevi

Source: https://archive.org/







Related documents