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 - Publisher Copyright:
© 2020 The Royal Society of Chemistry.
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.
UR - http://www.scopus.com/inward/record.url?scp=85078434338&partnerID=8YFLogxK
U2 - 10.1039/c9nr09572a
DO - 10.1039/c9nr09572a
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C2 - 31904048
AN - SCOPUS:85078434338
SN - 2040-3364
VL - 12
SP - 1894
EP - 1903
JO - Nanoscale
JF - Nanoscale
IS - 3
ER -