Deciphering the universe of genetic context-dependencies using mouse models of cancer

Falcomatà, Chiara; Bärthel, Stefanie; Schneider, Günter; Saur, Dieter; Veltkamp, Christian

doi:10.1016/j.gde.2019.04.002

Cited by 2 publications

(3 citation statements)

References 60 publications

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“…Besides the changes in the cancer cells, the surrounding environment is shaped by complex interactions between various different cell types, including subclonal cancer populations, immune cell subsets, and different stromal cell types (e.g., fibroblast subtypes, endothelial cells, or nerves). It has been shown that the TME is a critical driver of tumor evolution, intratumoral heterogeneity and therapeutic response and resistance; however, the specific genetic manipulation and therapeutic validation of cancer and TME cell subpopulations and the investigation of their interactions remained challenging ( 9 ).…”

Section: Dissecting the Functional Role Of Cancer And Tme Cell Subpop...mentioning

confidence: 99%

“…Another approach is to combine more than two orthogonal SSRs in one organism. Using three or more recombinases in an in vivo cancer model would allow for example the targeting of cell types, which are not characterized by a single marker gene, such as subsets of specialized immune cells or fibroblasts ( 9 ). One important limitation, especially in the case of more than two recombinase systems, is however the time and effort needed to breed cancer models harbouring multiple alleles.…”

Section: Current Limitations and Future Prospectsmentioning

confidence: 99%

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Dual Recombinase–Based Mouse Models Help Decipher Cancer Biology and Targets for Therapy

2023

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The advent of next-generation sequencing (NGS) and single-cell profiling technologies has revealed the complex and heterogenous ecosystem of human tumors under steady-state and therapeutic perturbation. Breakthroughs in the development of genetically engineered mouse models (GEMM) of human cancers that are based on the combination of two site-specific recombinase systems [dual-recombinase system (DRS)] offer fundamental new possibilities to elucidate and understand critical drivers of the diverse tumor phenotypes and validate potential targets for therapy. Here, we discuss opportunities DRS-based cancer GEMMs offer to model, trace, manipulate, and functionally investigate established cancers, their interactions with the host, and their response to therapy.

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Section: Dissecting the Functional Role Of Cancer And Tme Cell Subpop...mentioning

confidence: 99%

Section: Current Limitations and Future Prospectsmentioning

confidence: 99%

Dual Recombinase–Based Mouse Models Help Decipher Cancer Biology and Targets for Therapy

2023

Self Cite

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“…Tumor growth is strictly associated with the expansion of vasculature that supplies oxygen and nutrients to the tumor tissue and allows metastatic spread to colonize distant organs. It was shown that the tumor microenvironment (TME) composition as well as its functionality are tissue dependent and context dependent [9]. A useful approach to understand the impact of TME on tumor evolution is the genetically engineered mouse model (GEMM).…”

Section: Introductionmentioning

confidence: 99%

IBTK Haploinsufficiency Affects the Tumor Microenvironment of Myc-Driven Lymphoma in E-myc Mice

Vecchio

Fiume

Mignogna

et al. 2020

IJMS

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The tumor microenvironment is a dynamic and interactive supporting network of various components, including blood vessels, cytokines, chemokines, and immune cells, which sustain the tumor cell’s survival and growth. Murine models of lymphoma are useful to study tumor biology, the microenvironment, and mechanisms of response to therapy. Lymphomas are heterogeneous hematologic malignancies, and the complex microenvironment from which they arise and their multifaceted genetic basis represents a challenge for the generation and use of an appropriate murine model. So, it is important to choose the correct methodology. Recently, we supported the first evidence on the pro-oncogenic action of IBTK in Myc-driven B cell lymphomagenesis in mice, inhibiting apoptosis in the pre-cancerous stage. We used the transgenic Eμ-myc mouse model of non-Hodgkin’s lymphoma and Ibtk hemizygous mice to evaluate the tumor development of Myc-driven lymphoma. Here, we report that the allelic loss of Ibtk alters the immunophenotype of Myc-driven B cell lymphomas, increasing the rate of pre-B cells and affecting the tumor microenvironment in Eμ-myc mice. In particular, we observed enhanced tumor angiogenesis, increasing pro-angiogenic and lymphangiogenic factors, such as VEGF, MMP-9, CCL2, and VEGFD, and a significant recruitment of tumor-associated macrophages in lymphomas of Ibtk+/- Eμ-myc compared to Ibtk+/+ Eμ-myc mice. In summary, these results indicate that IBTK haploinsufficiency promotes Myc tumor development by modifying the tumor microenvironment.

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Deciphering the universe of genetic context-dependencies using mouse models of cancer

Cited by 2 publications

References 60 publications

Dual Recombinase–Based Mouse Models Help Decipher Cancer Biology and Targets for Therapy

Dual Recombinase–Based Mouse Models Help Decipher Cancer Biology and Targets for Therapy

IBTK Haploinsufficiency Affects the Tumor Microenvironment of Myc-Driven Lymphoma in E-myc Mice

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