A Novel Ex Vivo Tumor Spheroid-Tissue Model for Investigating Microvascular Remodeling and Lymphatic Blood Vessel Plasticity.
Angiogenesis
Biomimetic cancer model
Lymphatic/blood vessel plasticity
Mesentery
Tumor spheroid
Journal
Annals of biomedical engineering
ISSN: 1573-9686
Titre abrégé: Ann Biomed Eng
Pays: United States
ID NLM: 0361512
Informations de publication
Date de publication:
25 May 2024
25 May 2024
Historique:
received:
12
12
2023
accepted:
02
05
2024
medline:
26
5
2024
pubmed:
26
5
2024
entrez:
25
5
2024
Statut:
aheadofprint
Résumé
Biomimetic tumor microenvironment models bridge the gap between in vitro and in vivo systems and serve as a useful way to address the modeling challenge of how to recreate the cell and system complexity associated with real tissues. Our laboratory has developed an ex vivo rat mesentery culture model, which allows for simultaneous investigation of blood and lymphatic microvascular network remodeling in an intact tissue environment. Given that angiogenesis and lymphangiogenesis are key contributors to the progression of cancer, the objective of this study was to combine tissue and tumor spheroid culture methods to establish a novel ex vivo tumor spheroid-tissue model by verifying its use for evaluating the effects of cancer cell behavior on the local microvascular environment. H1299 or A549 tumor spheroids were formed via hanging drop culture and seeded onto rat mesenteric tissues harvested from adult male Wistar rats. Tissues with transplanted spheroids were cultured in serum-free media for 3 to 5 days. PECAM, NG2, CD11b, and αSMA labeling identified endothelial cells, pericytes, immune cells, and smooth muscle cells, respectively. Time-lapse imaging confirmed cancer cell type specific migration. In addition to increasing PECAM positive capillary sprouting and LYVE-1 positive endothelial cell extensions indicative of lymphangiogenesis, tumor spheroid presence induced the formation of lymphatic/blood vessel connections and the formation of hybrid, mosaic vessels that were characterized by discontinuous LYVE-1 labeling. The results support the application of a novel tumor spheroid microenvironment model for investigating cancer cell-microvascular interactions.
Identifiants
pubmed: 38796670
doi: 10.1007/s10439-024-03535-8
pii: 10.1007/s10439-024-03535-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Center, University of Florida Health
ID : 00096885 CA-FY22-03
Organisme : American Heart Association
ID : Grant 23TPA1142184
Organisme : National Science Foundation
ID : 1845728
Informations de copyright
© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.
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