NDLI: Spheroid-plug model as a tool to study tumor development, angiogenesis, and heterogeneity in vivo

Content Provider	Springer Nature Link
Author	Szade, Krzysztof Zukowska, Monika Szade, Agata Collet, Guillaume Kloska, Damian Kieda, Claudine Jozkowicz, Alicja Dulak, Jozef
Copyright Year	2015
Abstract	Subcutaneous injection of the tumor cell suspension is a simple and commonly used tool for studying tumor development in vivo. However, subcutaneous models poorly resemble tumor complexity due to the fast growth not reflecting the natural course. Here, we describe an application of the new spheroid-plug model to combine the simplicity of subcutaneous injection with improved resemblance to natural tumor progression. Spheroid-plug model relies on in vitro formation of tumor spheroids, followed by injection of single tumor spheroid subcutaneously in Matrigel matrix. In spheroid-plug model, tumors grow slower in comparison to tumors formed by injection of cell suspension as assessed by 3D ultrasonography (USG) and in vivo bioluminescence measurements. The slower tumor growth rate in spheroid-plug model is accompanied by reduced necrosis. The spheroid-plug model ensures increased and more stable vascularization of tumor than classical subcutaneous tumor model as demonstrated by 3D USG Power Doppler examination. Flow cytometry analysis showed that tumors formed from spheroids have enhanced infiltration of endothelial cells as well as hematopoietic and progenitor cells with stem cell phenotype (c-Kit$^{+}$ and Sca-1$^{+}$). They also contain more tumor cells expressing cancer stem cell marker CXCR4. Here, we show that spheroid-plug model allows investigating efficiency of anticancer drugs. Treatment of spheroid-plug tumors with known antiangiogenic agent axitinib decreased their size and viability. The antiangiogenic activity of axitinib was higher in spheroid-plug model than in classical model. Our results indicate that spheroid-plug model imitates natural tumor growth and can become a valuable tool for cancer research.
Starting Page	2481
Ending Page	2496
Page Count	16
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	2
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2015-09-18
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Cancer stem cells Necrosis Tumor infiltration Tumor vascularization B16 melanoma Lewis lung carcinoma (LLC) Tumor complexity Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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