Various CAM tumor models

Komatsu, Aoi; Higashi, Yuya; Matsumoto, Kotaro

doi:10.1016/bs.enz.2019.10.001

Cited by 15 publications

(10 citation statements)

References 37 publications

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“…Although tumors have been already successfully established on the CAM [4,[20][21][22][23][24][25][26][27][28][29], and PET-imaging studies are available [10,24,25,[30][31][32][33][34][35], systematic analyses of their use to evaluate the biodistribution of radiopharmaceuticals and direct comparisons with the in vivo gold standard are still rare [10].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Quantification of Target-Specific Accumulation of [18F]F-siPSMA-14 in the HET-CAM Model and in Mice Using PET/MRI

Löffler

Hamp

Scheidhauer

et al. 2021

Cancers

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Assessment of biodistribution and specific tumor accumulation is essential for the development of new radiopharmaceuticals and requires animal experiments. The HET-CAM (hens-egg test—chorioallantoic membrane) model can be used in combination with the non-invasive imaging modalities PET and MRI for pre-selection during radiopharmaceutical development to reduce the number of animal experiments required. Critical to the acceptance of this model is the demonstration of the quantifiability and reproducibility of these data compared to the standard animal model. Tumor accumulation and biodistribution of the PSMA-specific radiotracer [18F]F-siPSMA-14 was analyzed in the chick embryo and in an immunodeficient mouse model. Evaluation was based on MRI and PET data in both models. γ-counter measurements and histopathological analyses complemented these data. PSMA-specific accumulation of [18F]F-siPSMA-14 was successfully demonstrated in the HET-CAM model, similar to the results obtained by mouse model studies. The combination of MR and PET imaging allowed precise quantification of peptide accumulation, initial assessment of biodistribution, and accurate determination of tumor volume. Thus, the use of the HET-CAM model is suitable for the pre-selection of new radiopharmaceuticals and potentially reduces animal testing in line with the 3Rs principles of animal welfare.

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Section: Introductionmentioning

confidence: 99%

Comparison of Quantification of Target-Specific Accumulation of [18F]F-siPSMA-14 in the HET-CAM Model and in Mice Using PET/MRI

Löffler

Hamp

Scheidhauer

et al. 2021

Cancers

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“…To investigate the molecular mechanisms of oncogenicity in FP-RMS we characterised the initial cellular and molecular steps associated with the transformation of cells expressing PAX3-FOXO1 and PAX7-FOXO1. The growing evidence for an embryonic origin of paediatric cancers [ 35 ], the identification of FP-RMS growths in neural tube derived tissues [ 36 , 37 ], the recurrent presence of embryonic neural lineage determinants in FP-RMS cells [ 9 ], and the recent use of chick embryos to study cancer cells migration and invasion [ 38 , 39 ] led us to develop the embryonic chick neural tube as a model system. We demonstrate that PAX-FOXO1s repress the molecular hallmarks of neural tube progenitors within 48 hours and impose a molecular signature reminiscent of that of FP-RMS cells.…”

Section: Introductionmentioning

confidence: 99%

The PAX-FOXO1s trigger fast trans-differentiation of chick embryonic neural cells into alveolar rhabdomyosarcoma with tissue invasive properties limited by S phase entry inhibition

et al. 2020

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The chromosome translocations generating PAX3-FOXO1 and PAX7-FOXO1 chimeric proteins are the primary hallmarks of the paediatric fusion-positive alveolar subtype of Rhabdomyosarcoma (FP-RMS). Despite the ability of these transcription factors to remodel chromatin landscapes and promote the expression of tumour driver genes, they only inefficiently promote malignant transformation in vivo. The reason for this is unclear. To address this, we developed an in ovo model to follow the response of spinal cord progenitors to PAX-FOXO1s. Our data demonstrate that PAX-FOXO1s, but not wild-type PAX3 or PAX7, trigger the trans-differentiation of neural cells into FP-RMS-like cells with myogenic characteristics. In parallel, PAX-FOXO1s remodel the neural pseudo-stratified epithelium into a cohesive mesenchyme capable of tissue invasion. Surprisingly, expression of PAX-FOXO1s, similar to wild-type PAX3/7, reduce the levels of CDK-CYCLIN activity and increase the fraction of cells in G1. Introduction of CYCLIN D1 or MYCN overcomes this PAX-FOXO1-mediated cell cycle inhibition and promotes tumour growth. Together, our findings reveal a mechanism that can explain the apparent limited oncogenicity of PAX-FOXO1 fusion transcription factors. They are also consistent with certain clinical reports indicative of a neural origin of FP-RMS.

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“…To investigate the molecular mechanisms of oncogenicity in ARMS we characterised the initial cellular and molecular steps associated with the transformation of cells expressing PAX3FOXO1 and PAX7FOXO1. The growing evidence for an embryonic origin of paediatric cancers [35], the identification of ARMS growths in neural tube derived tissues [36,37], the recurrent presence of embryonic neural lineage determinants in ARMS cells [9], and the recent use of chick embryos to study cancer cells migration and invasion [38,39] led us to develop the embryonic chick neural tube as a model system. We demonstrate that PAXFOXO1s repress the molecular hallmarks of neural tube progenitors within 48 hours and impose a molecular signature reminiscent of that of ARMS cells.…”

Section: Introductionmentioning

confidence: 99%

The PAXFOXO1s trigger fast trans-differentiation of chick embryonic neural cells into alveolar rhabdomyosarcoma with tissue invasive properties limited by S phase entry inhibition

Curto

Vartanian

Frarma

et al. 2020

Preprint

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The chromosome translocations generating PAX3FOXO1 and PAX7FOXO1 chimeric proteins are the primary hallmarks of the paediatric cancer, Alveolar Rhabdomyosarcoma (ARMS).Despite the ability of these transcription factors to remodel chromatin landscapes and promote the expression of tumour driver genes, they only inefficiently promote malignant transformation in vivo. The reason for this is unclear. To address this, we developed an in ovo model to follow the response of spinal cord progenitors to PAXFOXO1s. Our data demonstrate that PAXFOXO1s, but not wild-type PAX3 and PAX7, trigger the trans-differentiation of neural cells into ARMS-like cells with myogenic characteristics. In parallel expression of PAXFOXO1s remodels the neural pseudo-stratified epithelium into a cohesive mesenchyme capable of tissue invasion. Surprisingly, gain for PAXFOXO1s, as for wild-type PAX3/7, reduces the levels of CDK-CYCLIN activity and arrests cells in G1. Introduction of CYCLIN D1 or MYCN overcomes PAXFOXO1s mediated cell cycle inhibition and promotes tumour growth. Together, our findings reveal a mechanism underpinning the apparent limited oncogenicity of PAXFOXO1 fusion transcription factors and support a neural origin for ARMS.We deeply thank the ImagoSeine core facility of Institut Jacques Monod, a member of France-BioImaging (ANR-10-INBS-04) and certified IBiSA. We thank Griselda Wentzinger and Magali Fradet for performing cell sorting at ImagoSeine Institut Jacques Monod platform. We are grateful to the people who have provided us with useful tools. We received plasmids from

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Various CAM tumor models

Cited by 15 publications

References 37 publications

Comparison of Quantification of Target-Specific Accumulation of [18F]F-siPSMA-14 in the HET-CAM Model and in Mice Using PET/MRI

Comparison of Quantification of Target-Specific Accumulation of [18F]F-siPSMA-14 in the HET-CAM Model and in Mice Using PET/MRI

The PAX-FOXO1s trigger fast trans-differentiation of chick embryonic neural cells into alveolar rhabdomyosarcoma with tissue invasive properties limited by S phase entry inhibition

The PAXFOXO1s trigger fast trans-differentiation of chick embryonic neural cells into alveolar rhabdomyosarcoma with tissue invasive properties limited by S phase entry inhibition

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