| 1. |
- Heldin, Paraskevi, et al.
(författare)
-
Deregulation of hyaluronan synthesis, degradation and binding promotes breast cancer
- 2013
-
Ingår i: Journal of Biochemistry (Tokyo). - : Oxford University Press (OUP). - 0021-924X .- 1756-2651. ; 154:5, s. 395-408
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical and experimental data indicate that hyaluronan accumulates in breast cancer compared with normal breast epithelium, which correlates to poor prognosis. In this review, we discuss the expression of genes encoding enzymes that synthesize or degrade hyaluronan, i.e. hyaluronan synthases and hyaluronidases or bind hyaluronan, i.e. CD44 and receptor for hyaluronan-mediated motility (RHAMM, also designated as HMMR or CD168), in relation to breast cancer progression. Hyaluronan and hyaluronan receptors have multi-faceted roles in signalling events in breast cancer. A better understanding of the molecular mechanisms underlying these signalling pathways is highly warranted and may lead to improvement of cancer treatment.
|
|
| 2. |
- Olofsson, Berit, et al.
(författare)
-
Knock-Down of CD44 Regulates Endothelial Cell Differentiation via NF kappa B-Mediated Chemokine Production
- 2014
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3, s. e90921-
-
Tidskriftsartikel (refereegranskat)abstract
- A 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.
|
|
| 3. |
- Porsch, Helena, et al.
(författare)
-
Platelet-derived Growth Factor beta-Receptor, Transforming Growth Factor beta Type I Receptor, and CD44 Protein Modulate Each Other's Signaling and Stability
- 2014
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 289:28, s. 19747-19757
-
Tidskriftsartikel (refereegranskat)abstract
- Growth factors, such as platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta(TGF beta), are key regulators of cellular functions, including proliferation, migration, and differentiation. Growth factor signaling is modulated by context-dependent cross-talk between different signaling pathways. We demonstrate in this study that PDGF-BB induces phosphorylation of Smad2, a downstream mediator of the canonical TGF beta pathway, in primary dermal fibroblasts. The PDGF-BB-mediated Smad2 phosphorylation was dependent on the kinase activities of both TGF beta type I receptor (T beta RI) and PDGF beta-receptor (PDGFR beta), and it was prevented by inhibitory antibodies against TGF beta. Inhibition of the activity of the T beta RI kinase greatly reduced the PDGF-BB-dependent migration in dermal fibroblasts. Moreover, we demonstrate that the receptors for PDGF-BB and TGF beta interact physically in primary dermal fibroblasts and that stimulation with PDGF-BB induces internalization not only of PDGFR beta but also of T beta RI. In addition, silencing of PDGFR beta by siRNA decreased the stability of T beta RI and delayed TGF beta-induced signaling. We further show that the hyaluronan receptor CD44 interacts with both PDGFR beta and T beta RI. Depletion of CD44 by siRNA increased signaling via PDGFR beta and T beta RI by stabilizing the receptor proteins. Our data suggest that cross-talk between PDGFR beta and T beta RI occurs in dermal fibroblasts and that CD44 negatively modulates signaling via these receptors.
|
|
| 4. |
|
|
