Comparison of Three Transcytotic Pathways for Distribution to Brain Metastases of Breast Cancer.
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
04 05 2023
04 05 2023
Historique:
received:
20
12
2022
revised:
07
02
2023
accepted:
08
03
2023
medline:
5
5
2023
pubmed:
14
3
2023
entrez:
13
3
2023
Statut:
ppublish
Résumé
Advances in drug treatments for brain metastases of breast cancer have improved progression-free survival but new, more efficacious strategies are needed. Most chemotherapeutic drugs infiltrate brain metastases by moving between brain capillary endothelial cells, paracellular distribution, resulting in heterogeneous distribution, lower than that of systemic metastases. Herein, we tested three well-known transcytotic pathways through brain capillary endothelial cells as potential avenues for drug access: transferrin receptor (TfR) peptide, low-density lipoprotein receptor 1 (LRP1) peptide, albumin. Each was far-red labeled, injected into two hematogenous models of brain metastases, circulated for two different times, and their uptake quantified in metastases and uninvolved (nonmetastatic) brain. Surprisingly, all three pathways demonstrated distinct distribution patterns in vivo. Two were suboptimal: TfR distributed to uninvolved brain but poorly in metastases, while LRP1 was poorly distributed. Albumin distributed to virtually all metastases in both model systems, significantly greater than in uninvolved brain (P < 0.0001). Further experiments revealed that albumin entered both macrometastases and micrometastases, the targets of treatment and prevention translational strategies. Albumin uptake into brain metastases was not correlated with the uptake of a paracellular probe (biocytin). We identified a novel mechanism of albumin endocytosis through the endothelia of brain metastases consistent with clathrin-independent endocytosis (CIE), involving the neonatal Fc receptor, galectin-3, and glycosphingolipids. Components of the CIE process were found on metastatic endothelial cells in human craniotomies. The data suggest a reconsideration of albumin as a translational mechanism for improved drug delivery to brain metastases and possibly other central nervous system (CNS) cancers.In conclusion, drug therapy for brain metastasis needs improvement. We surveyed three transcytotic pathways as potential delivery systems in brain-tropic models and found that albumin has optimal properties. Albumin used a novel endocytic mechanism.
Identifiants
pubmed: 36912773
pii: 718745
doi: 10.1158/1535-7163.MCT-22-0815
pmc: PMC10164055
mid: NIHMS1883960
doi:
Substances chimiques
Peptides
0
Albumins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
646-658Subventions
Organisme : NCI NIH HHS
ID : HHSN261201500003C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201500003I
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 BC010538
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 SC000892
Pays : United States
Informations de copyright
©2023 American Association for Cancer Research.
Références
Eur J Neurosci. 2011 Oct;34(7):1062-73
pubmed: 21899600
Int J Mol Sci. 2020 Jun 21;21(12):
pubmed: 32575812
Glycobiology. 2015 Apr;25(4):351-6
pubmed: 25715344
Oncotarget. 2016 Jun 7;7(23):34038-51
pubmed: 27086917
Pharm Res. 2016 Dec;33(12):2904-2919
pubmed: 27541873
J Cereb Blood Flow Metab. 2016 Apr;36(4):731-42
pubmed: 26661181
Nat Commun. 2018 Jul 13;9(1):2705
pubmed: 30006619
Sci Transl Med. 2022 May 4;14(643):eabl3649
pubmed: 35507675
Nature. 2010 Nov 25;468(7323):562-6
pubmed: 20944625
Front Immunol. 2019 Jul 10;10:1540
pubmed: 31354709
Nat Rev Cancer. 2020 Jan;20(1):4-11
pubmed: 31780784
J Neurocytol. 1991 Dec;20(12):998-1006
pubmed: 1783946
Clin Cancer Res. 2020 Jun 15;26(12):2789-2799
pubmed: 31969331
Nat Rev Clin Oncol. 2021 Nov;18(11):696-714
pubmed: 34253912
J Neurocytol. 1996 Nov;25(11):645-57
pubmed: 9013426
J Biol Chem. 2009 Mar 27;284(13):8292-300
pubmed: 19164298
Nat Rev Dis Primers. 2019 Jan 17;5(1):5
pubmed: 30655533
Prog Neurobiol. 2019 Oct;181:101665
pubmed: 31376426
Sci Rep. 2022 Nov 29;12(1):20537
pubmed: 36446793
Eur J Pharm Sci. 2013 Jul 16;49(4):556-64
pubmed: 23748097
Cancer Res. 2007 May 1;67(9):4190-8
pubmed: 17483330
Oncotarget. 2017 Jul 26;8(48):83734-83744
pubmed: 29137378
J Control Release. 2012 Jan 10;157(1):4-28
pubmed: 21959118
Sci Transl Med. 2011 May 25;3(84):84ra44
pubmed: 21613623
Expert Opin Drug Deliv. 2017 Feb;14(2):141-153
pubmed: 27935765
Breast Cancer Res Treat. 2016 Jun;157(2):307-318
pubmed: 27167986
Chem Soc Rev. 2016 Mar 7;45(5):1432-56
pubmed: 26771036
Pharm Res. 2012 Mar;29(3):770-81
pubmed: 22011930
J Clin Oncol. 2020 Aug 10;38(23):2610-2619
pubmed: 32468955
ACS Appl Mater Interfaces. 2018 Sep 12;10(36):30201-30213
pubmed: 30113810
Neuro Oncol. 2020 Nov 26;22(11):1625-1636
pubmed: 32386414
Int J Clin Oncol. 2009 Aug;14(4):299-306
pubmed: 19705239
Pharm Res. 2009 Nov;26(11):2486-94
pubmed: 19774344
Pharmacol Rev. 2006 Mar;58(1):32-45
pubmed: 16507881
Clin Cancer Res. 2010 Dec 1;16(23):5664-78
pubmed: 20829328
J Cereb Blood Flow Metab. 2016 May;36(5):862-90
pubmed: 26868179
Cell Mol Life Sci. 2019 Mar;76(6):1081-1092
pubmed: 30523362
FEBS J. 2015 Nov;282(21):4067-79
pubmed: 26277326
J Control Release. 2012 Jul 20;161(2):429-45
pubmed: 22155554
J Neurochem. 1998 Sep;71(3):1151-7
pubmed: 9721740
Otol Neurotol. 2020 Jan;41(1):123-132
pubmed: 31568132
Front Immunol. 2015 Jan 26;5:682
pubmed: 25674083
Cancer. 1992 Feb 15;69(4):972-80
pubmed: 1735089
Clin Cancer Res. 2014 May 15;20(10):2727-39
pubmed: 24634373
Pharm Res. 2012 Jul;29(7):1949-59
pubmed: 22399388
Nature. 2020 Apr;580(7803):381-385
pubmed: 32296178
Nat Cell Biol. 2014 Jun;16(6):595-606
pubmed: 24837829
Neuron. 2014 May 7;82(3):603-17
pubmed: 24746419