bioluminescent-orthotopic-model-of-pancreatic-cancer-progression

Bioluminescent Orthotopic Model of Pancreatic Cancer Progression

Pancreatic cancer has an extremely poor five-year survival rate of 4-6%.  New therapeutic options are critically needed and depend on improved ...

Monash University

Lymphatic metastasis is facilitated by lymphangiogenic growth factors VEGF-C and VEGF-D that are secreted by some primary tumors. We identified regulation of PGDH, the key enzyme in prostaglandin catabolism, in endothelial cells of collecting lymphatics, as a key molecular change during VEGF-D-driven tumor spread. The VEGF-D-dependent regulation of the prostaglandin pathway was supported by the finding that collecting lymphatic vessel dilation and subsequent metastasis were affected by nonsteroidal anti-inflammatory drugs (NSAIDs), known inhibitors of prostaglandin synthesis. Our data suggest a control point for cancer metastasis within the collecting lymphatic endothelium, which links VEGF-D/VEGFR-2/VEGFR-3 and the prostaglandin pathways. Collecting lymphatics therefore play an active and important role in metastasis and may provide a therapeutic target to restrict tumor spread.

VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium.

M&eacute;tastase lymphatique est facilit&eacute;e par des facteurs de croissance lymphangiog&eacute;nique VEGF-C et VEGF-D qui sont s&eacute;cr&eacute;t&eacute;es par certaines tumeurs primaires. Nous avons identifi&eacute; le r&egrave;glement de PGDH, l&#39;enzyme cl&eacute; du catabolisme de prostaglandine, dans les cellules endoth&eacute;liales de la collecte des vaisseaux lymphatiques, comme un changement mol&eacute;culaire cl&eacute; au cours de la propagation de la tumeur de VEGF-D-conduit. La r&eacute;gulation de VEGF-D-d&eacute;pendant de la voie de la prostaglandine a &eacute;t&eacute; &eacute;tay&eacute;e par le fait que collecte dilatation de vaisseau lymphatique et m&eacute;tastase ult&eacute;rieur ont &eacute;t&eacute; affect&eacute;es par les anti-inflammatoires non st&eacute;ro&iuml;diens (AINS), connu des inhibiteurs de la synth&egrave;se des prostaglandines. Nos donn&eacute;es sugg&egrave;rent un point de contr&ocirc;le pour les m&eacute;tastases du cancer dans l&#39;endoth&eacute;lium lymphatique gestion collective, qui relie le VEGF-D/VEGFR-2/VEGFR-3 et les voies de la prostaglandine. Collecteurs de vaisseaux lymphatiques donc jouent un r&ocirc;le actif et important dans les m&eacute;tastases et peuvent fournir une cible th&eacute;rapeutique visant &agrave; limiter la propagation de la tumeur.

VEGF-D favorise les m&eacute;tastases tumorales en r&eacute;glementant les prostaglandines produites par l&#39;endoth&eacute;lium lymphatique collecte.

Metastasi linfatiche sono facilitata da fattori di crescita lymphangiogenic VEGF-C e VEGF-D che sono secreti da alcuni tumori primari. Abbiamo identificato regolamento di PGDH, l&#39;enzima chiave nel catabolismo delle prostaglandine, nelle cellule endoteliali di raccolta di vasi linfatici, come un cambiamento molecolare chiave durante la diffusione del tumore VEGF-D-driven. Il regolamento di VEGF-D-dipendente del percorso prostaglandina &egrave; stato sostenuto dalla constatazione che raccogliendo la dilatazione del vaso linfatico e metastasi successive sono stati influenzati da farmaci anti-infiammatori non steroidei (FANS), noti inibitori della sintesi della prostaglandina. I nostri dati suggeriscono un punto di controllo per metastasi del cancro all&#39;interno della raccolta endotelio linfatico, che collega i percorsi della prostaglandina e VEGF-D/VEGFR-2/VEGFR-3. Raccolta di vasi linfatici pertanto svolgono un ruolo attivo e importante in metastasi e possono fornire un obiettivo terapeutico per limitare la diffusione del tumore.

Ming G. Chai

Monash Institute of Pharmaceutical Sciences

Monash University

Bioluminescent Orthotopic Model of Pancreatic Cancer Progression

Ming G. Chai

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Monash Institute of Pharmaceutical Sciences

Monash University

Bioluminescent Orthotopic Model of Pancreatic Cancer Progression

Monash Institute of Pharmaceutical Sciences