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Reduction of liver metastasis stiffness improves response to bevacizumab in metastatic colorectal cancer

Tumors are influenced by the mechanical properties of their microenvironment. Using patient samples and atomic force microscopy, we found that tissue stiffness is higher in liver metastases than in primary colorectal tumors. Highly activated metastasis-associated fibroblasts increase tissue stiffnes...

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Main Authors: Shen, Ying (Author) , Wang, Xiaohong (Author) , Lu, Junyan (Author) , Salfenmoser, Martin (Author) , Wirsik, Naita Maren (Author) , Schleußner, Nikolai (Author) , Imle, Andrea (Author) , Freire Valls, Aida (Author) , Radhakrishnan, Praveen (Author) , Liang, Jie (Author) , Wang, Guoliang (Author) , Muley, Thomas (Author) , Schneider, Martin (Author) , Ruiz de Almodóvar, Carmen (Author) , Diz Muñoz, Alba (Author) , Schmidt, Thomas (Author)
Format: Article (Journal)
Language:English
Published: June 8, 2020
In: Cancer cell
Year: 2020, Volume: 37, Issue: 6, Pages: 800-817
ISSN:1878-3686
DOI:10.1016/j.ccell.2020.05.005
Online Access:Verlag, lizenzpflichtig, Volltext: http://dx.doi.org/10.1016/j.ccell.2020.05.005
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Author Notes:Ying Shen, Xiaohong Wang, Junyan Lu, Martin Salfenmoser, Naita Maren Wirsik, Nikolai Schleussner, Andrea Imle, Aida Freire Valls, Praveen Radhakrishnan, Jie Liang, Guoliang Wang, Thomas Muley, Martin Schneider, Carmen Ruiz de Almodovar, Alba Diz-Muñoz, and Thomas Schmidt
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Summary:Tumors are influenced by the mechanical properties of their microenvironment. Using patient samples and atomic force microscopy, we found that tissue stiffness is higher in liver metastases than in primary colorectal tumors. Highly activated metastasis-associated fibroblasts increase tissue stiffness, which enhances angiogenesis and anti-angiogenic therapy resistance. Drugs targeting the renin-angiotensin system, normally prescribed to treat hypertension, inhibit fibroblast contraction and extracellular matrix deposition, thereby reducing liver metastases stiffening and increasing the anti-angiogenic effects of bevacizumab. Patients treated with bevacizumab showed prolonged survival when concomitantly treated with renin-angiotensin inhibitors, highlighting the importance of modulating the mechanical microenvironment for therapeutic regimens.
Item Description:Gesehen am 14.07.2020
Physical Description:Online Resource
ISSN:1878-3686
DOI:10.1016/j.ccell.2020.05.005

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