VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium (Cancer Cell, 2012, 21:181-195)

報告日期: 2012/11/16
報告時間: 17:10/18:00
報告學生: 李脩琦
講評老師: 呂佩融
附件下載: 下載[1246-1348734547-1.pdf] 

 

VEGF-D Promotes Tumor Metastasis by Regulating Prostaglandins Produced by the Collecting Lymphatic Endothelium

Cancer Cell 21, 181–195, February 14, 2012

Date: 2012/11/16

Speaker: Hsiu-Chi Lee

Commentator: Pei-Jung Frank Lu, Ph.D

Abstract

The tumor cells entering into the lymphatic system and subsequent spreading to lymphatic node is an important sign for cancer metastasis and disease staging.   The sentinel lymph node (SLN) is hypothetically the first lymph node or group of nodes draining a cancer.  The collecting lymphatic vessel (CLV) collects lymph from lymph capillaries and drains into lymph nodes.  The data from clinical samples suggest that peritumoral lymphatic vessels are important for metastasis and patient outcome.  Previous study has shown that tumor-secreted lymphangiogenic growth factors, vascular endothelial growth factor (VEGF) –C or –D, promote tumor lymphatics formation and raise the rate of metastasis of lymphatic node.  However, the impact of lymphangiogenic growth factors on the CLV draining the primary tumor to SLN is poorly understood.  In this study, the author investigated the mechanism of alteration of CLV by VEGF-D-driven metastasis model.  They found that VEGF-D changes the CLV diameter, possibly to promote tumor spread via VEGF receptor-2 and -3 heterdimer signaling.  The VEGF-D/VEGFR-2/VEGFR-3-signalling axes downregulated a key enzyme for balancing prostaglandin (PGs) catabolism, 15-hydroxyprostaglandin dehydrogenase (PGDH), which increases the PGs level, especially PGE2.  These results suggested that VEGF-D-activated VEGFR-2/VEGFR-3 is capable of regulating the level of vasodilatory PGs and morphological change of CLV.  In addition, the author utilized anti-VEGFR-2 and -3 antibodies and anti-inflammatory drugs (NSAIDs) as strategy to reverse morphological change of CLV.  These data provide anti-cancer metastasis knowledge within CLV, which was linked to VEGF-D signaling and prostaglandin pathways. 

Reference

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2.     Shayan, R., Achen, M.G., and Stacker, S.A. (2006).  Lymphatic vessels in cancer metastasis: bridging the gaps. Carcinogenesis vol.27 no.9 pp.1729–1738.