Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic Approaches

Cancers
Janette BeshayHolger Weber

Abstract

In this second study, we established syngeneic in vivo models named carcinogen-induced mouse-derived isografts (cMDIs). Carcinogen-induced tumors were obtained during short-term observation (3⁻9 months) of CBA/J mice treated with various administration routes with 3-methylcholanthrene (MCA) or N-methyl-N-nitrosourea (MNU) as carcinogens. During necropsy, primary tumors and suspicious tissues were assessed macroscopically and re-transplanted (in PDX-like manner) into sex-matched syngeneic animals. Outgrowing tumors were histologically characterized as either spinocellular carcinoma (1/8) or various differentiated sarcomas (7/8). Growth curves of four sarcomas showed striking heterogeneity. These cMDIs were further characterized by flow cytometry, RNA sequencing, or efficacy studies. A variable invasion of immune cells into the tumors, as well as varying expression of tyrosine kinase receptor, IFN-γ signature, or immune cell population marker genes could be observed. Immune checkpoint inhibitor treatment (anti-mPD-1, anti-mCTLA-4, or a combination thereof) showed different responses in the various cMDI models. In general, cMDI models are carcinogen-induced tumors of low passage number that were propagated as tissue pieces in mice...Continue Reading

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Citations

Jun 13, 2020·International Journal of Molecular Sciences·Daria S ChulpanovaValeriya V Solovyeva

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Methods Mentioned

BETA
genetic modifications
flow
RNA-Seq
flow cytometry
FACS

Software Mentioned

MS
GraphPad
Excel
GraphPad Prism

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