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

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