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Longitudinal bioluminescence imaging to monitor breast tumor growth and treatment response using the chick chorioallantoic membrane model.

ABSTRACT: The development of successful treatment regimens for breast cancer requires strong pre-clinical data generated in physiologically relevant pre-clinical models. Here we report the development of the chick embryo chorioallantoic membrane (CAM) model to study tumor growth and angiogenesis using breast cancer cell lines. MDA-MB-231 and MCF7 tumor cell lines were engrafted onto the chick embryo CAM to study tumor growth and treatment response. Tumor growth was evaluated through bioluminescence imaging and a significant increase in tumor size and vascularization was found over a 9-day period. We then evaluated the impact of anti-angiogenic drugs, axitinib and bevacizumab, on tumor growth and angiogenesis. Drug treatment significantly reduced tumor vascularization and size. Overall, our findings demonstrate that the chick embryo CAM is a clinically relevant model to monitor therapeutic response in breast cancer and can be used as a platform for drug screening to evaluate not only gross changes in tumor burden but physiological processes such as angiogenesis.

SUBMITTER: Javed S

PROVIDER: S-EPMC9562337 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Longitudinal bioluminescence imaging to monitor breast tumor growth and treatment response using the chick chorioallantoic membrane model.

Javed Sumreen S Soukhtehzari Sepideh S Fernandes Nazarine N Williams Karla C KC

Scientific reports 20221013 1

The development of successful treatment regimens for breast cancer requires strong pre-clinical data generated in physiologically relevant pre-clinical models. Here we report the development of the chick embryo chorioallantoic membrane (CAM) model to study tumor growth and angiogenesis using breast cancer cell lines. MDA-MB-231 and MCF7 tumor cell lines were engrafted onto the chick embryo CAM to study tumor growth and treatment response. Tumor growth was evaluated through bioluminescence imagin ...[more]

PMID: 36229503

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Project description:Our previous study demonstrated that the expression of miR‑146a‑5p was downregulated in non‑small cell lung cancer (NSCLC) tissue, which affected the progression and prognosis of patients with NSCLC. Thus, the present study was conducted to investigate the functional mechanism of miR‑146a‑5p in tumorigenesis and angiogenesis in NSCLC. Following the construction of a H460 NSCLC cell line in which miR‑146a‑5p was overexpressed via lentivirus transduction, the NSCLC chick embryo chorioallantoic membrane (CAM) model was established by transplanting miR‑146a‑5p‑overexpressing NSCLC cells into the CAM. Then, the size of the neoplasms within the CAM was measured, the vessel ratio was calculated, and the cellular morphology, metastasis and inflammation of tumor cell was observed using hematoxylin and eosin staining. The target genes of miR‑146a‑5p were predicted by 12 online software programs; these genes were then subjected to Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway annotations using the Database for Annotation, Visualization and Integrated Discovery 6.7 as well as constructed into a protein interaction network using protein‑protein interaction from Search Tool for the Retrieval of Interacting Genes/Proteins. The xenograft tumor size and angiogenesis conditions of the miR‑146a‑5p‑overexpressing group (volume 6.340±0.066 mm3, vessel ratio 9.326±0.083) was obviously restricted (P<0.001) when compared with the low expression group (volume 30.13±0.06 mm3, vessel ratio 16.94±0.11). In addition, marked necrosis along with inflammatory cell infiltration was observed with the HE‑stained slices from the miR‑146a‑5p low expression group. Regarding the results of the target gene prediction, cancer and toll‑like receptor signaling were the two most significant pathways represented among the target genes, while JUN, EGFR and RAC1 were the most relevant proteins among the selected potential targets of miR‑146a‑5p. In a CAM xenograft tumor model, overexpression of miR‑146a‑5p inhibited the tumorigenesis and angiogenesis of an NSCLC cell line. miR‑146a‑5p may act as a tumor suppressor gene in NSCLC and have moderate prognostic value in lung cancer.

Project description:The chick embryo chorioallantoic membrane (CAM) tumor model is a valuable preclinical model for studying the tumor-colonizing process of Salmonella enterica serovar Typhimurium. It offers advantages such as cost-effectiveness, rapid turnaround, reduced engraftment issues, and ease of observation. In this study, we explored and validated the applicability of the partially immune-deficient CAM tumor model. Herein, we demonstrate that Salmonella preferentially colonizes tumors and directly causes tumor cell death. Bacterial migration, tumor colonization, and intra-tumor distribution did not require flagellar-mediated motility. The vast majority of Salmonella that colonized the CAM tumor were extracellular. Thus, tumor invasion was independent of both Salmonella pathogenicity island-1-encoded and Salmonella pathogenicity island-2-encoded type III secretion systems. Surprisingly, the extracellular residence of Salmonella on CAM tumors did not require biofilm formation. We evaluated our wild-type parental strain compared to the attenuated clinical strain VNP20009 and discovered a reduced tumor colonization capability of VNP20009. The inability to effectively colonize CAM tumors potentially explains the reduced anti-tumor efficacy of VNP20009. Our work establishes the xenograft CAM model as an informative and predictive screening platform for studying tumor-colonizing Salmonella.IMPORTANCECancer has a major impact on society, as it poses a significant health burden to human populations worldwide. Salmonella Typhimurium has demonstrated promise in cancer treatment by exerting direct tumoricidal effects and enhancing host-mediated anti-tumor immunity in xenograft mouse studies. A general understanding of its pathogenesis and the relative ease of genetic manipulation support the development of attenuated strains for therapeutic use. Alternative in ovo models, such as the chorioallantoic membrane tumor model, present a suitable screening platform to accelerate the development of therapeutic strains. It allows for rapid evaluation of Salmonella strains to assess their efficacy and potential as oncolytic agents. The present study establishes that the in ovo tumor model can be utilized as a preclinical tool for evaluating oncolytic Salmonella, bridging the gap between in vitro and in vivo screening.

Project description:ObjectivesThis study was designed to verify the antiangiogenic activity of ferulic acid (FA) and its potency to inhibit cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) expression in the chorioallantoic membrane (CAM) model. Moreover, we verified its mechanism of action by docking the molecule on COX-2, tyrosine kinase, and VEGF-2 proteins in silico.Materials and methodsAn antiangiogenesis assay of FA at doses of 30, 60, and 90 μg was performed using the CAM of chicken eggs that were 9 days old and stimulated by 60 ng of basic fibroblast growth factor. Celecoxib (60 μg) was used as the reference drug. The inhibitory activity on VEGF and COX-2 expression was determined by immunohistochemistry assay. Molecular docking of FA was accomplished by Molegro Virtual Docker program ver. 5.5 on COX-2 enzyme (PDB ID 1CX2), tyrosine kinase receptor (PDB ID 1XKK), and VEGF-2 receptor (PDB ID 4ASD).ResultsFA at doses of 30, 60, and 90 μg significantly prevented angiogenesis in the CAM model, which was represented as inhibitory activity against endothelial cells of blood vessels (42.6-70.7%) and neovascularization (43.0-86.6%). The inhibitory activity of FA against VEGF expression was stronger than its action on COX-2 expression. Molecular docking on VEGF-2 receptor resulted in an RS value of FA of -73.844 kcal/mol and for celecoxib it was -94.557 kcal/mol. The RS value on tyrosine kinase of FA was -84.954 kcal/mol, while on celecoxib it was -93.163 kcal/mol. Docking on COX-2 receptor gave an RS value of FA of -73.416 kcal/mol, while for celecoxib it was -118.107 kcal/mol.ConclusionReductions in VEGF-2 and COX-2 expression due to treatment with FA at the dose range 30-90 μg appeared to be related to angiogenesis inhibition, which was shown by two parameters, namely inhibition of neovascularization and endothelial cell growth in blood vessels. It was concluded that FA is a promising antiangiogenic therapeutic agent especially at the early stage, and this activity can arise from inhibitory action on COX-2 and VEGF-2 proteins.

Dataset Information

Longitudinal bioluminescence imaging to monitor breast tumor growth and treatment response using the chick chorioallantoic membrane model.

Publications

Longitudinal bioluminescence imaging to monitor breast tumor growth and treatment response using the chick chorioallantoic membrane model.

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