IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v4y2013i1d10.1038_ncomms3516.html
   My bibliography  Save this article

Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels

Author

Listed:
  • Vikash P. Chauhan

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School
    School of Engineering and Applied Sciences, Harvard University)

  • John D. Martin

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School
    Massachusetts Institute of Technology)

  • Hao Liu

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School
    Program in Biological and Biomedical Sciences, Harvard Medical School)

  • Delphine A. Lacorre

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School)

  • Saloni R. Jain

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School
    Massachusetts Institute of Technology)

  • Sergey V. Kozin

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School)

  • Triantafyllos Stylianopoulos

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School
    University of Cyprus)

  • Ahmed S. Mousa

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School)

  • Xiaoxing Han

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School)

  • Pichet Adstamongkonkul

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School
    School of Engineering and Applied Sciences, Harvard University)

  • Zoran Popović

    (Massachusetts Institute of Technology)

  • Peigen Huang

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School)

  • Moungi G. Bawendi

    (Massachusetts Institute of Technology)

  • Yves Boucher

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School)

  • Rakesh K. Jain

    (Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School)

Abstract

Cancer 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.

Suggested Citation

  • Vikash P. Chauhan & John D. Martin & Hao Liu & Delphine A. Lacorre & Saloni R. Jain & Sergey V. Kozin & Triantafyllos Stylianopoulos & Ahmed S. Mousa & Xiaoxing Han & Pichet Adstamongkonkul & Zoran Po, 2013. "Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3516
    DOI: 10.1038/ncomms3516
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms3516
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/ncomms3516?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Guiraldello, Rafael T. & Martins, Marcelo L. & Mancera, Paulo F.A., 2016. "Evaluating the efficacies of Maximum Tolerated Dose and metronomic chemotherapies: A mathematical approach," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 456(C), pages 145-156.
    2. Duk Ki Kim & Juhee Jeong & Dong Sun Lee & Do Young Hyeon & Geon Woo Park & Suwan Jeon & Kyung Bun Lee & Jin-Young Jang & Daehee Hwang & Ho Min Kim & Keehoon Jung, 2022. "PD-L1-directed PlGF/VEGF blockade synergizes with chemotherapy by targeting CD141+ cancer-associated fibroblasts in pancreatic cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    3. Yen-Ho Lai & Chia-Yu Su & Hung-Wei Cheng & Chao-Yi Chu & Long-Bin Jeng & Chih-Sheng Chiang & Woei-Cherng Shyu & San-Yuan Chen, 2023. "Stem cell–nanomedicine system as a theranostic bio-gadolinium agent for targeted neutron capture cancer therapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Myrofora Panagi & Fotios Mpekris & Pengwen Chen & Chrysovalantis Voutouri & Yasuhiro Nakagawa & John D. Martin & Tetsuro Hiroi & Hiroko Hashimoto & Philippos Demetriou & Chryso Pierides & Rekha Samuel, 2022. "Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Paiva, L.R. & Ferreira, S.C. & Martins, M.L., 2016. "Effects of vascularization on cancer nanochemotherapy outcomes," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 455(C), pages 79-91.
    6. Maxim Kuznetsov, 2021. "Combined Influence of Nutrient Supply Level and Tissue Mechanical Properties on Benign Tumor Growth as Revealed by Mathematical Modeling," Mathematics, MDPI, vol. 9(18), pages 1-27, September.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3516. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.