TY - JOUR
T1 - An ovarian spheroid based tumor model that represents vascularized tumors and enables the investigation of nanomedicine therapeutics
AU - Singh, Manu Smriti
AU - Goldsmith, Meir
AU - Thakur, Kavita
AU - Chatterjee, Sushmita
AU - Landesman-Milo, Dalit
AU - Levy, Tally
AU - Kunz-Schughart, Leoni A.
AU - Barenholz, Yechezkel
AU - Peer, Dan
N1 - Funding Information:
This work was supported in part by the Israel Science Foundation (ISF) grant # 1178/16, the Rivkin Foundation and the Len and Susan Mark program in Ovarian Cancer awarded to D. P. M. S. S. would like to thank Centre for Nanoscience and Nanotechnology, Tel Aviv University for awarding travel grant as a visiting fellow at OncoRay – Center for Radiation Research in Oncology, Faculty of Medicine, Technical University, Dresden.
Publisher Copyright:
© 2020 The Royal Society of Chemistry.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/1/21
Y1 - 2020/1/21
N2 - The failure of cancer therapies in clinical settings is often attributed to the lack of a relevant tumor model and pathological heterogeneity across tumor types in the clinic. The objective of this study was to develop a robust in vivo tumor model that better represents clinical tumors for the evaluation of anti-cancer therapies. We successfully developed a simple mouse tumor model based on 3D cell culture by injecting a single spheroid and compared it to a tumor model routinely used by injecting cell suspension from 2D monolayer cell culture. We further characterized both tumors with cellular markers for the presence of myofibroblasts, pericytes, endothelial cells and extracellular matrix to understand the role of the tumor microenvironment. We further investigated the effect of chemotherapy (doxorubicin), nanomedicine (Doxil®), biological therapy (Avastin®) and their combination. Our results showed that the substantial blood vasculature in the 3D spheroid model enhances the delivery of Doxil® by 2.5-fold as compared to the 2D model. Taken together, our data suggest that the 3D tumors created by simple subcutaneous spheroid injection represents a robust and more vascular murine tumor model which is a clinically relevant platform to test anti-cancer therapy in solid tumors.
AB - The failure of cancer therapies in clinical settings is often attributed to the lack of a relevant tumor model and pathological heterogeneity across tumor types in the clinic. The objective of this study was to develop a robust in vivo tumor model that better represents clinical tumors for the evaluation of anti-cancer therapies. We successfully developed a simple mouse tumor model based on 3D cell culture by injecting a single spheroid and compared it to a tumor model routinely used by injecting cell suspension from 2D monolayer cell culture. We further characterized both tumors with cellular markers for the presence of myofibroblasts, pericytes, endothelial cells and extracellular matrix to understand the role of the tumor microenvironment. We further investigated the effect of chemotherapy (doxorubicin), nanomedicine (Doxil®), biological therapy (Avastin®) and their combination. Our results showed that the substantial blood vasculature in the 3D spheroid model enhances the delivery of Doxil® by 2.5-fold as compared to the 2D model. Taken together, our data suggest that the 3D tumors created by simple subcutaneous spheroid injection represents a robust and more vascular murine tumor model which is a clinically relevant platform to test anti-cancer therapy in solid tumors.
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U2 - 10.1039/c9nr09572a
DO - 10.1039/c9nr09572a
M3 - Article
C2 - 31904048
AN - SCOPUS:85078434338
VL - 12
SP - 1894
EP - 1903
JO - Nanoscale
JF - Nanoscale
SN - 2040-3364
IS - 3
ER -