Study shows how NSAIDs inhibit lymphatic metastasis

Abstract

www.thelancet.com/oncology Vol 13 April 2012 e144 A new study investigating lymphatic metastasis has led to a possible explanation for the eff ectiveness of non-steroidal anti-infl ammatory drugs (NSAIDs) as anti-cancer agents. Researchers at the Peter MacCallum Cancer Centre (Melbourne, VIC, Australia) used mouse xenograft models of lymphogenous spread to show how VEGF-D secreted by primary tumours induces dilation of collecting lymphatic vessels during metastasis by downregulating the expression of the enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH), the key function of which is the degradation of prostaglandins. They showed that NSAIDs could be used to inhibit VEGFD-driven metastasis by interfering with the prostaglandin pathway and blocking lymphatic vessel dilation. Steven Stacker (Peter MacCallum Cancer Centre), co-author of the study, told The Lancet Oncology: “our data suggest that NSAIDs could restrict the rate of metastatic spread of tumour cells by reducing the dilation of collecting lymphatics, particularly in epithelial cancers such as gastrointestinal, breast, prostate and lung, which are more likely to metastasise through the lymphatic system”. “Given that restricting or blocking metastatic spread is a critical factor in ensuring cancer survival, adapting NSAID treatment to reduce metastasis should lead to fewer deaths”, Stacker added. Commenting on the research, Peter Rothwell (University of Oxford, Oxford, UK) said: “there is evidence that aspirin, and possibly other NSAIDs, might reduce blood-borne metastasis, but these new fi ndings are interesting in that they suggest a possible mechanism for an eff ect on lymphatic spread”. “Clinical evidence of an eff ect of aspirin or NSAIDs on risk of metastasis is mainly limited to observational studies and appears to be stronger for distant metastasis than for local and regional metastasis, but small eff ects on lymphatic spread have not been excluded”, Rothwell continued. Discussing previous clinical research, Stacker said: “We believe our data are consistent with the fi ndings of longterm randomised trials using NSAIDs, which found that cancer deaths were reduced in patients treated with aspirin”. John Burn (Newcastle University, Newcastle upon Tyne, UK) said that “this is an exciting and important report which off ers one mechanism for the observed benefi ts of aspirin as an adjuvant treatment in colorectal cancer”. He added: “it adds weight to the case for aspirin use as a routine adjuvant in addition to the growing case for its use as a chemopreventive in those with increased genetic risk”.