• 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • Expression of DDR in endothelial cells has been


    Expression of DDR1 in endothelial cells has been previously described in human corneal blood vessels, and more recently, in murine atherosclerotic plaques (Franco et al., 2008, Mohan et al., 2001). So far, there is a lack of evidence for DDR1 expression in endothelial cells in the mouse BRD 7552 (Franco-Pons et al., 2006). Interestingly, in the present study, we detected only the N-terminal extracellular domain of this molecule in the endothelial cells of the human brain. The role of DDR1 in endothelial cells may be to transmit a signal following the activation of a downstream signaling cascade by collagen (Vogel et al., 2006). Supporting this model, it has been shown that the α2β1 integrin I receptor and DDR1 coordinately upregulate the expression of N-cadherin in response to collagen I, promoting tumor pancreatic cell scattering (Shintani et al., 2008). We detected full-length DDR1 in the soma of only certain astrocytes and oligodendrocytes, indicating that this receptor may be expressed in these cells only under particular circumstances, i.e., after activation of the cells by exogenous molecules such as growth factors and cytokines (Matsuyama et al., 2004) or other exogenous stimuli. For example, rat astrocyte DDR1b is induced following ionizing radiation (Sakuma et al., 1996). In turn, DDR1 may be expressed only when the cell needs to stop its migratory and proliferative activities while entering cell-cycle arrest (Vogel et al., 2006, Yeh et al., 2009). It is reasonable to hypothesize that collagen may be the ligand that induces DDR1 activation under such circumstances.
    Experimental procedures
    Acknowledgments This study was supported in part by grants from the Stanley Medical Research Institute (#03R-392 and #05R-896), the , research grant #PI020498) and the Spanish Ministry of Science (research grant #MICINN, SAF2007-60086, funding FEDER).
    Introduction Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the fifth-most prevalent but the second-most lethal cancer worldwide (Karaman et al., 2014). In most cases HCC developed after chronic liver disease caused by various factors such as viral hepatitis B/C alcohol or metabolic syndrome (Zucman-Rossi et al., 2015). Due to frequent late diagnosis, the prognosis for HCC is poor. HCC invasion criteria such as satellite nodules, vascular embolization or capsule invasion are hallmark features of HCC progression. This intra or extra-liver metastasis formation participates to the very high HCC mortality rate because they cause liver failure and their presence is not compatible with liver transplantation. Therefore, it is crucial to decipher molecular mechanisms used by HCC cells to invade and colonize liver, vessels and distant organs. Transforming growth factor-β1 (TGF-β1) is an important player BRD 7552 in chronic liver diseases inducing fibrogenesis and tumorigenesis (Giannelli et al., 2014). TGF-β1 is involved in HCC development and progression (Neuzillet et al., 2014). High levels of this inflammatory factor were measured in plasma of HCC patients compared to patients with cirrhosis only (Ito et al., 1991, Shirai et al., 1994). This growth factor is secreted by hepatic stellate cells, myofibroblasts and cancer-associated fibroblasts during fibrosis or HCC (Dooley and ten Dijke, 2012). TGF-β1 promotes pleiotropic modifications at the cellular and matrix microenvironment levels (Giannelli et al., 2014) and participates to the progression of liver diseases (Dooley and ten Dijke, 2012). It regulates many cellular pathways and is involved in epithelial-mesenchymal transition (EMT) (Lamouille et al., 2014). It regulates E-cadherin expression, activates β1 integrin and promotes HCC cell migration and invasion (Fransvea et al., 2008, Fransvea et al., 2009). In the canonical pathway, TGF-β1 binds to TGF-β1 receptor (TGF-βRI) inducing the phosphorylation of Smad2/3 proteins. Phosphorylated Smad2/3 form a complex with a common mediator, Smad4, which translocates to the nucleus and regulates gene transcription through the interaction with various transcription factors.