Reduction of Liver Metastasis Stiffness Improves Response to Bevacizumab in Metastatic Colorectal Cancer.
Angiogenesis Inhibitors
/ pharmacology
Angiotensin II Type 1 Receptor Blockers
/ pharmacology
Angiotensin-Converting Enzyme Inhibitors
/ pharmacology
Bevacizumab
/ pharmacology
Cancer-Associated Fibroblasts
/ drug effects
Captopril
/ pharmacology
Colorectal Neoplasms
/ drug therapy
Drug Synergism
Humans
Liver Neoplasms
/ drug therapy
Losartan
/ pharmacology
Lung Neoplasms
/ drug therapy
Neovascularization, Pathologic
/ prevention & control
Renin-Angiotensin System
/ drug effects
Tumor Microenvironment
/ drug effects
CAFs
MAFs
RAS signaling
anti-angiogenic therapy
atomic force microscopy
bevacizumab
fibroblasts
metastatic colorectal cancer
tissue stiffness
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
08 06 2020
08 06 2020
Historique:
received:
26
11
2018
revised:
12
02
2020
accepted:
06
05
2020
entrez:
10
6
2020
pubmed:
10
6
2020
medline:
4
11
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32516590
pii: S1535-6108(20)30255-5
doi: 10.1016/j.ccell.2020.05.005
pii:
doi:
Substances chimiques
Angiogenesis Inhibitors
0
Angiotensin II Type 1 Receptor Blockers
0
Angiotensin-Converting Enzyme Inhibitors
0
Bevacizumab
2S9ZZM9Q9V
Captopril
9G64RSX1XD
Losartan
JMS50MPO89
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
800-817.e7Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.