Show simple item record Bridgeman VL Vermeulen PB Foo S Bilecz, Ágnes Daley F Kostaras E Nathan MR Wan E Frentzas S Schweiger T Hegedűs, Balázs Hoetzenecker K Rényi-Vámos, Ferenc István Kuczynski EA Vasudev NS Larkin J Gore M Dvorak HF Paku, Sándor Kerbel RS Döme, Balázs Reynolds AR 2018-06-11T09:06:21Z 2018-06-11T09:06:21Z 2017
dc.identifier 85006889134
dc.identifier.citation pagination=362-374; journalVolume=241; journalIssueNumber=3; journalTitle=JOURNAL OF PATHOLOGY;
dc.identifier.uri doi:10.1002/path.4845
dc.description.abstract Anti-angiogenic therapies have shown limited efficacy in the clinical management of metastatic disease, including lung metastases. Moreover, the mechanisms via which tumours resist anti-angiogenic therapies are poorly understood. Importantly, rather than utilising angiogenesis, some metastases may instead incorporate pre-existing vessels from surrounding tissue (vessel co-option). Since anti-angiogenic therapies were designed to target only new blood vessel growth, vessel co-option has been proposed as a mechanism that could drive resistance to anti-angiogenic therapy. However, vessel co-option has not been extensively studied in lung metastases, and its potential to mediate resistance to anti-angiogenic therapy in lung metastases is not established. Here we examine the mechanism of tumour vascularisation in 164 human lung metastasis specimens (composed of breast, colorectal and renal cancer lung metastasis cases). We identify four distinct histopathological growth patterns (HGPs) of lung metastasis (alveolar, interstitial, perivascular cuffing and pushing) that each vascularise via a different mechanism. In the alveolar HGP, cancer cells invade the alveolar air spaces, which facilitates the co-option of alveolar capillaries. In the interstitial HGP, cancer cells invade into the alveolar walls to co-opt alveolar capillaries. In the perivascular cuffing HGP, cancer cells grow by co-opting larger vessels of the lung. Only in the pushing HGP did the tumours vascularise by angiogenesis. Importantly, vessel co-option occurred with high frequency, being present in over 80% of the cases examined. Moreover, we provide evidence that vessel co-option mediates resistance to the anti-angiogenic drug sunitinib in preclinical lung metastasis models. Assuming that our interpretation of the data is correct, we conclude that vessel co-option in lung metastases occurs through at least three distinct mechanisms, that vessel co-option occurs frequently in lung metastases and that vessel co-option could mediate resistance to anti-angiogenic therapy in lung metastases. Novel therapies designed to target both angiogenesis and vessel co-option are therefore warranted.
dc.relation.ispartof urn:issn:0022-3417
dc.title Vessel co-option is common in human lung metastases and mediates resistance to anti-angiogenic therapy in preclinical lung metastasis models
dc.type Journal Article 2018-06-06T12:22:43Z
dc.language.rfc3066 en
dc.identifier.mtmt 3140936
dc.identifier.wos 000393863900006
dc.identifier.pubmed 27859259
dc.contributor.department SE/AOK/K/Mellkassebészeti Klinika
dc.contributor.department SE/AOK/I/II. Sz. Patológiai Intézet
dc.contributor.department SE/AOK/I/IISZPI/MTA-SE Molekuláris Onkológia Kutatócsoport
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote Balazs Dome and Andrew R Reynolds Equal contributions.

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