Vascular response patterns to targeted therapies in murine breast cancer models with divergent degrees of malignancy.

Animals Mice Sorafenib Neoplasms Immunotherapy Albumins Cognition Tumor Microenvironment
Immune checkpoint inhibition Magnetic resonance imaging Sorafenib Targeted therapy Tumor microenvironment Tumor vasculature

Journal

Breast cancer research : BCR
ISSN: 1465-542X
Titre abrégé: Breast Cancer Res
Pays: England
ID NLM: 100927353

Informations de publication

Date de publication:
23 05 2023
Historique:
received: 06 01 2023
accepted: 14 05 2023
medline: 25 5 2023
pubmed: 24 5 2023
entrez: 24 5 2023
Statut: epublish

Résumé

Response assessment of targeted cancer therapies is becoming increasingly challenging, as it is not adequately assessable with conventional morphological and volumetric analyses of tumor lesions. The tumor microenvironment is particularly constituted by tumor vasculature which is altered by various targeted therapies. The aim of this study was to noninvasively assess changes in tumor perfusion and vessel permeability after targeted therapy in murine models of breast cancer with divergent degrees of malignancy. Low malignant 67NR or highly malignant 4T1 tumor-bearing mice were treated with either the multi-kinase inhibitor sorafenib or immune checkpoint inhibitors (ICI, combination of anti-PD1 and anti-CTLA4). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with i.v. injection of albumin-binding gadofosveset was conducted on a 9.4 T small animal MRI. Ex vivo validation of MRI results was achieved by transmission electron microscopy, immunohistochemistry and laser ablation-inductively coupled plasma-mass spectrometry. Therapy-induced changes in tumor vasculature differed between low and highly malignant tumors. Sorafenib treatment led to decreased tumor perfusion and endothelial permeability in low malignant 67NR tumors. In contrast, highly malignant 4T1 tumors demonstrated characteristics of a transient window of vascular normalization with an increase in tumor perfusion and permeability early after therapy initiation, followed by decreased perfusion and permeability parameters. In the low malignant 67NR model, ICI treatment also mediated vessel-stabilizing effects with decreased tumor perfusion and permeability, while ICI-treated 4T1 tumors exhibited increasing tumor perfusion with excessive vascular leakage. DCE-MRI enables noninvasive assessment of early changes in tumor vasculature after targeted therapies, revealing different response patterns between tumors with divergent degrees of malignancy. DCE-derived tumor perfusion and permeability parameters may serve as vascular biomarkers that allow for repetitive examination of response to antiangiogenic treatment or immunotherapy.

Sections du résumé

BACKGROUND
Response assessment of targeted cancer therapies is becoming increasingly challenging, as it is not adequately assessable with conventional morphological and volumetric analyses of tumor lesions. The tumor microenvironment is particularly constituted by tumor vasculature which is altered by various targeted therapies. The aim of this study was to noninvasively assess changes in tumor perfusion and vessel permeability after targeted therapy in murine models of breast cancer with divergent degrees of malignancy.
METHODS
Low malignant 67NR or highly malignant 4T1 tumor-bearing mice were treated with either the multi-kinase inhibitor sorafenib or immune checkpoint inhibitors (ICI, combination of anti-PD1 and anti-CTLA4). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with i.v. injection of albumin-binding gadofosveset was conducted on a 9.4 T small animal MRI. Ex vivo validation of MRI results was achieved by transmission electron microscopy, immunohistochemistry and laser ablation-inductively coupled plasma-mass spectrometry.
RESULTS
Therapy-induced changes in tumor vasculature differed between low and highly malignant tumors. Sorafenib treatment led to decreased tumor perfusion and endothelial permeability in low malignant 67NR tumors. In contrast, highly malignant 4T1 tumors demonstrated characteristics of a transient window of vascular normalization with an increase in tumor perfusion and permeability early after therapy initiation, followed by decreased perfusion and permeability parameters. In the low malignant 67NR model, ICI treatment also mediated vessel-stabilizing effects with decreased tumor perfusion and permeability, while ICI-treated 4T1 tumors exhibited increasing tumor perfusion with excessive vascular leakage.
CONCLUSION
DCE-MRI enables noninvasive assessment of early changes in tumor vasculature after targeted therapies, revealing different response patterns between tumors with divergent degrees of malignancy. DCE-derived tumor perfusion and permeability parameters may serve as vascular biomarkers that allow for repetitive examination of response to antiangiogenic treatment or immunotherapy.

Identifiants

DOI: 10.1186/s13058-023-01658-9 PMID: 37221619 PMC: PMC10207609
pubmed: 37221619
doi: 10.1186/s13058-023-01658-9
pii: 10.1186/s13058-023-01658-9
pmc: PMC10207609
doi:

Substances chimiques

Sorafenib 9ZOQ3TZI87
Albumins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

56

Informations de copyright

© 2023. The Author(s).

Références

Front Oncol. 2021 Aug 12;11:719836
pubmed: 34476218
Front Immunol. 2020 May 07;11:784
pubmed: 32457745
Magn Reson Med. 2008 Dec;60(6):1313-20
pubmed: 19030165
Physiol Rev. 2011 Jul;91(3):1071-121
pubmed: 21742796
Z Med Phys. 2008;18(2):85-90
pubmed: 18705608
PLoS One. 2015 Jun 22;10(6):e0131095
pubmed: 26098849
Br J Radiol. 2015 Sep;88(1053):20150163
pubmed: 26133222
Oncotarget. 2017 Nov 21;9(15):11964-11976
pubmed: 29552285
J Nucl Med. 2015 Mar;56(3):450-6
pubmed: 25678492
Proc Natl Acad Sci U S A. 2014 Aug 12;111(32):11774-9
pubmed: 25071169
Cell Mol Life Sci. 2020 May;77(9):1745-1770
pubmed: 31690961
Anticancer Agents Med Chem. 2021;21(1):3-19
pubmed: 32807068
Front Oncol. 2020 Feb 27;10:221
pubmed: 32175278
Transl Oncol. 2022 Jun;20:101405
pubmed: 35339889
Arch Pathol Lab Med. 2012 May;136(5):483-9
pubmed: 22229850
J Immunother Cancer. 2021 Sep;9(9):
pubmed: 34561275
Mol Pharm. 2020 Jan 6;17(1):109-117
pubmed: 31816245
Mol Imaging Biol. 2020 Feb;22(1):66-72
pubmed: 31098983
Eur J Radiol. 2012 May;81(5):891-6
pubmed: 21889860
Front Oncol. 2013 Aug 15;3:211
pubmed: 23967403
J Clin Med. 2019 Dec 29;9(1):
pubmed: 31905724
Diagn Interv Radiol. 2010 Sep;16(3):186-92
pubmed: 19885783
Clin Mol Hepatol. 2014 Jun;20(2):218-22
pubmed: 25032190
Korean J Radiol. 2014 Sep-Oct;15(5):554-77
pubmed: 25246817
J Clin Invest. 2018 May 1;128(5):2104-2115
pubmed: 29664018
Proc Natl Acad Sci U S A. 2012 May 15;109(20):7841-6
pubmed: 22547817
Eur J Cancer. 2011 Jan;47(2):277-86
pubmed: 20863686
Radiology. 2008 May;247(2):391-9
pubmed: 18372448
Cancer Res. 2021 Jul 1;81(13):3693-3705
pubmed: 33837042
Front Cell Dev Biol. 2022 Mar 29;10:885670
pubmed: 35425768
Biomed Pharmacother. 2021 Jul;139:111607
pubmed: 33965730
Cancer Drug Resist. 2019 Sep 19;2(3):595-607
pubmed: 35582580
GE Port J Gastroenterol. 2019 Jul;26(4):260-267
pubmed: 31328140
PLoS One. 2020 Jun 10;15(6):e0234520
pubmed: 32520950
Br J Cancer. 2021 Jul;125(2):164-175
pubmed: 33824479
Semin Thromb Hemost. 2010 Apr;36(3):321-31
pubmed: 20490982
J Immunother Cancer. 2021 Mar;9(3):
pubmed: 33712445
Cancer Microenviron. 2013 Apr;6(1):1-17
pubmed: 22467426
Expert Opin Drug Deliv. 2011 Apr;8(4):485-504
pubmed: 21338327
Cancer Treat Rev. 2011 Feb;37(1):63-74
pubmed: 20570444
N Engl J Med. 1971 Nov 18;285(21):1182-6
pubmed: 4938153
Cancer Imaging. 2013 Dec 16;13(4):557-66
pubmed: 24380871
Cancers (Basel). 2021 Apr 06;13(7):
pubmed: 33917287
Front Oncol. 2018 Sep 10;8:367
pubmed: 30250827
Cell. 2000 Jan 7;100(1):57-70
pubmed: 10647931
J Magn Reson Imaging. 2005 Oct;22(4):511-9
pubmed: 16161072
Nat Rev Clin Oncol. 2019 Jul;16(7):442-458
pubmed: 30718844
Am J Clin Pathol. 2015 Feb;143(2):177-85; quiz 305
pubmed: 25596243
Front Oncol. 2022 Nov 02;12:1000036
pubmed: 36408159
Cells. 2022 Mar 10;11(6):
pubmed: 35326400
Cancer Treat Rev. 2017 Feb;53:98-110
pubmed: 28088074
Oncotarget. 2017 Nov 6;8(63):107096-107108
pubmed: 29291014
Magn Reson Med. 2011 Sep;66(3):735-45
pubmed: 21384424
Int J Cancer. 2020 Mar 15;146(6):1730-1740
pubmed: 31840816
Target Oncol. 2017 Apr;12(2):243-253
pubmed: 28299600
Cell Death Dis. 2018 Jan 25;9(2):115
pubmed: 29371595
Cytokine. 2011 Aug;55(2):251-9
pubmed: 21531574
Cancer Sci. 2008 Dec;99(12):2373-9
pubmed: 19018775

Auteurs

Emily Hoffmann (E)

Clinic of Radiology, University of Münster, Münster, Germany. emily.hoffmann@ukmuenster.de.
ORCID: 0000-0002-0958-6699

Mirjam Gerwing (M)

Clinic of Radiology, University of Münster, Münster, Germany.

Tobias Krähling (T)

Clinic of Radiology, University of Münster, Münster, Germany.

Uwe Hansen (U)

Institute for Musculoskeletal Medicine, University of Münster, Münster, Germany.

Katharina Kronenberg (K)

Institute of Inorganic and Analytical Chemistry, University of Münster, Münster, Germany.

Max Masthoff (M)

Clinic of Radiology, University of Münster, Münster, Germany.

Christiane Geyer (C)

Clinic of Radiology, University of Münster, Münster, Germany.

Carsten Höltke (C)

Clinic of Radiology, University of Münster, Münster, Germany.

Lydia Wachsmuth (L)

Clinic of Radiology, University of Münster, Münster, Germany.

Regina Schinner (R)

Department of Radiology, University Hospital, LMU Munich, Munich, Germany.

Verena Hoerr (V)

Clinic of Radiology, University of Münster, Münster, Germany.
Heart Center Bonn, Department of Internal Medicine II, University Hospital Bonn, Bonn, Germany.

Walter Heindel (W)

Clinic of Radiology, University of Münster, Münster, Germany.

Uwe Karst (U)

Institute of Inorganic and Analytical Chemistry, University of Münster, Münster, Germany.

Michel Eisenblätter (M)

Clinic of Radiology, University of Münster, Münster, Germany.
Department of Diagnostic and Interventional Radiology, Medical Faculty OWL, University of Bielefeld, Bielefeld, Germany.

Bastian Maus (B)

Clinic of Radiology, University of Münster, Münster, Germany.

Anne Helfen (A)

Clinic of Radiology, University of Münster, Münster, Germany.

Cornelius Faber (C)

Clinic of Radiology, University of Münster, Münster, Germany.

Moritz Wildgruber (M)

Clinic of Radiology, University of Münster, Münster, Germany.
Department of Radiology, University Hospital, LMU Munich, Munich, Germany.

Articles similaires

Evaluating the efficacy of telesurgery with dual console SSI Mantra Surgical Robotic System: experiment on animal model and clinical trials.

Sudhir Prem Srivastava, Vishwajyoti Pascual Srivastava, Avinesh Singh et al.
1.00
Robotic Surgical Procedures Animals Humans Telemedicine Models, Animal

Odour generalisation and detection dog training.

Lyn Caldicott, Thomas W Pike, Helen E Zulch et al.
1.00
Animals Odorants Dogs Generalization, Psychological Smell

FBXO22 inhibits colitis and colorectal carcinogenesis by regulating the degradation of the S2448-phosphorylated form of mTOR.

Minle Li, Xuan Chen, Pengfei Qu et al.
1.00
Animals TOR Serine-Threonine Kinases Colorectal Neoplasms Colitis Mice

Use of organic material provided by an automatic enrichment device by weaner pigs and its influence on tail lesions.

Philipp Heseker, Jeanette Probst, Stefanie Ammer et al.
1.00
Animals Tail Swine Behavior, Animal Animal Husbandry

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Vascular response patterns to targeted...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Vascular response patterns to targeted...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Acides nicotiniques › Nicotinamide › Sorafénib › Vascular response patterns to targeted...
questionsmedicales.fr › Tumeurs › Vascular response patterns to targeted...
questionsmedicales.fr › Thérapeutique › Biothérapie › Immunothérapie › Vascular response patterns to targeted...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Albumines › Vascular response patterns to targeted...
questionsmedicales.fr › Phénomènes psychologiques › Processus mentaux › Cognition › Vascular response patterns to targeted...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Vascular response patterns to targeted...