Abstract:
: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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Shen Y,Wang X,Lu J,Salfenmoser M,Wirsik NM,Schleussner N,Imle A,Freire Valls A,Radhakrishnan P,Liang J,Wang G,Muley T,Schneider M,Ruiz de Almodovar C,Diz-Muñoz A,Schmidt Tdoi
10.1016/j.ccell.2020.05.005subject
Has Abstractpub_date
2020-06-08 00:00:00pages
800-817.e7issue
6eissn
1535-6108issn
1878-3686pii
S1535-6108(20)30255-5journal_volume
37pub_type
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