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dc.contributor.authorChauhan, Vikash P.
dc.contributor.authorLiu, Hao
dc.contributor.authorLacorre, Delphine A.
dc.contributor.authorJain, Saloni R.
dc.contributor.authorKozin, Sergey V.
dc.contributor.authorStylianopoulos, Triantafyllos
dc.contributor.authorMousa, Ahmed S.
dc.contributor.authorHan, Xiaoxing
dc.contributor.authorAdstamongkonkul, Pichet
dc.contributor.authorHuang, Peigen
dc.contributor.authorBawendi, Moungi G.
dc.contributor.authorBoucher, Yves
dc.contributor.authorJain, Rakesh K.
dc.contributor.authorMartin, John Daniel
dc.contributor.authorPopovic, Zoran
dc.date.accessioned2013-11-25T17:20:30Z
dc.date.available2013-11-25T17:20:30Z
dc.date.issued2013-10
dc.date.submitted2013-07
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/1721.1/82573
dc.description.abstractCancer and stromal cells actively exert physical forces (solid stress) to compress tumour blood vessels, thus reducing vascular perfusion. Tumour interstitial matrix also contributes to solid stress, with hyaluronan implicated as the primary matrix molecule responsible for vessel compression because of its swelling behaviour. Here we show, unexpectedly, that hyaluronan compresses vessels only in collagen-rich tumours, suggesting that collagen and hyaluronan together are critical targets for decompressing tumour vessels. We demonstrate that the angiotensin inhibitor losartan reduces stromal collagen and hyaluronan production, associated with decreased expression of profibrotic signals TGF-β1, CCN2 and ET-1, downstream of angiotensin-II-receptor-1 inhibition. Consequently, losartan reduces solid stress in tumours resulting in increased vascular perfusion. Through this physical mechanism, losartan improves drug and oxygen delivery to tumours, thereby potentiating chemotherapy and reducing hypoxia in breast and pancreatic cancer models. Thus, angiotensin inhibitors—inexpensive drugs with decades of safe use—could be rapidly repurposed as cancer therapeutics.en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Grant P01-CA080124)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Grant R01-CA126642)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Grant R01-CA085140)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Grant R01-CA115767)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Grant R01-CA098706)en_US
dc.description.sponsorshipUnited States. Dept. of Defense. Breast Cancer Research Program (Innovator Award W81XWH-10-1-0016)en_US
dc.description.sponsorshipLustgarten Foundation (Dana-Farber Cancer Institute/David H. Koch Institute for Integrative Cancer Research at MIT Bridge Project Grant)en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/ncomms3516en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en_US
dc.sourcePMCen_US
dc.titleAngiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vesselsen_US
dc.typeArticleen_US
dc.identifier.citationChauhan, Vikash P., John D. Martin, Hao Liu, Delphine A. Lacorre, Saloni R. Jain, Sergey V. Kozin, Triantafyllos Stylianopoulos, et al. “Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels.” Nature Communications 4 (October 1, 2013). © 2013 Nature Publishing Group, a division of Macmillan Publishers Limiteden_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.mitauthorMartin, John Danielen_US
dc.contributor.mitauthorJain, Saloni R.en_US
dc.contributor.mitauthorPopovic, Zoranen_US
dc.contributor.mitauthorBawendi, Moungi G.en_US
dc.relation.journalNature Communicationsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsChauhan, Vikash P.; Martin, John D.; Liu, Hao; Lacorre, Delphine A.; Jain, Saloni R.; Kozin, Sergey V.; Stylianopoulos, Triantafyllos; Mousa, Ahmed S.; Han, Xiaoxing; Adstamongkonkul, Pichet; Popović, Zoran; Huang, Peigen; Bawendi, Moungi G.; Boucher, Yves; Jain, Rakesh K.en_US
dc.identifier.orcidhttps://orcid.org/0000-0003-2220-4365
mit.licensePUBLISHER_CCen_US


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