Fenofibrate enhances barrier function of endothelial continuum within the metastatic niche of prostate cancer cells

Abstract

(2015) Fenofibrate enhances barrier function of endothelial continuum within the metastatic niche of prostate cancer cells, Expert

Invasive Cx43high sub-line of human prostate DU145 cells displays increased nanomechanical deformability

“…DU145 cells were seeded at a density of 7 × 10 4 cells per well in a 12well plate in an antibiotic-free DMEM-F12 HAM medium supplemented with 10% FBS and grown overnight at 37ºC. MISSION ® esiRNA GJA1 (114 pmol, Sigma) and Lipofectamine TM 2000 (Invitrogen) were used for transient Cx43 silencing in the DU145_48 cells according to the manufacturer's protocol (Piwowarczyk et al, 2015). The efficiency of the inhibition of Cx43 expression was subsequently analysed by using immunoblotting.…”

Connexin-dependent intercellular stress signaling in tissue homeostasis and tumor development

“…Cx43 function during this process may be attributed to the disturbance of endothelial calcium homeostasis by GJIC-mediated calcium fluxes from tumor to endothelial cells (Lewalle et al, 1998). We have recently demonstrated that prostate cancer cells can also activate the "inside-out" stress signaling axis with endothelial cells in Cx43-dependent, GJIC-independent manner (Piwowarczyk et al, 2015;Piwowarczyk et al, 2017). Other studies showed increased apoptosis of endothelial cells in the proximity of tumor cells, however the involvement of connexin in this process still requires experimental verification.…”

“…Connexins and gap junctions apparently confer "inside-out" stress signaling from tumor cells to the stroma that favors tumor cell extravasation. Cx43 is involved in the diapedesis of melanoma, glioblastoma, breast, lung and gastric cancer cells (El Sabban & Pauli, 1991;El Sabban & Pauli, 1994;Ito et al, 2000;Zhang et al, 2003a;Pollmann et al, 2005;Naoi et al, 2007;Elzarrad et al, 2008;Tang et al, 2013;Piwowarczyk et al, 2015;Ryszawy et al, 2014). Cx43 function during this process may be attributed to the disturbance of endothelial calcium homeostasis by GJIC-mediated calcium fluxes from tumor to endothelial cells (Lewalle et al, 1998).…”

Fenofibrate inhibits tumour intravasation by several independent mechanisms in a 3-dimensional co-culture model

“…Importantly, not only cancer cells play an active role in this process but also lymph endothelial cells (LECs) remarkably contribute to lymph node metastasis i.e. by providing niches for cancer cell settlement (5). To further study the role of LECs at an early metastatic step, a quantitative assay based on a three-dimensional (3D) cell model was developed consisting of breast cancer spheroids placed on top of lymphendothelial monolayers, which resembles the contact zone between the…”