Inducible mouse models of colon cancer for the analysis of sporadic and inflammation-driven tumor progression and lymph node metastasis

Neufert, Clemens; Heichler, Christina; Brabletz, Thomas; Scheibe, Kristina; Boonsanay, Verawan; Greten, Florian R.

doi:10.1038/s41596-020-00412-1

Cited by 52 publications

(44 citation statements)

References 61 publications

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“…Colitis-related tumor is a lifelong complication of irritable bowel syndrome that can occur in both Crohn's dis-ease and psoriatic arthritis with colonic inclusion. Furthermore, ecological variables and lifestyle-associated elements like obesity, inactivity, and smoking have been linked to an increased risk of colon cancer [1]. The dried roots of Astragalus membranaceus (AM) is utilized to cure common colds, diarrhea, weariness, and anorexia.…”

Section: Introductionmentioning

confidence: 99%

The Effect and Related Mechanism of Action of Astragalus Compatible with Curcumin against Colon Cancer Metastasis in Mice

Tang

2022

Gastroenterology Research and Practice

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Colon cancer (CC) is the third most common tumor worldwide. Colon carcinogenesis is strongly linked to inflammation. The initiation and progression of colon cancer may be influenced by epigenetic processes. Cancer metastasis is a multistep process involving several genes and their products. During tumor metastasis, cancer cells first enhance their proliferative capacity by lowering autophagy and apoptosis, and then, their capacity is stimulated by boosting tumors’ ability to take nutrients from the outside via angiogenesis. Traditional treatment focuses on eliminating tumor cells by triggering cell death or activating the immune system, which often results in side effects or chemoresistance recurrence. On the contrary, Chinese medicine theory considers the patient’s entire inner system and aids in tumor shrinkage while also taking into account the mouse’ general health. Because many Chinese herbal medicines (CHM) are consumed as food, using edible CHMs as a diet resource therapy for colon cancer treatment is a viable option. Two traditional Chinese herbs, Astragalus membranaceus and Curcuma zedoaria, are commonly utilized jointly in colon cancer preventive therapy. As a result, the anticancer effect of astragalus and curcumin (AC) on colon cancer suppression in an 18-week AOM-DSS colon cancer mouse model is investigated in this research. These findings may offer a scientific foundation for investigating colon cancer diagnostic biomarkers and therapeutic application of AC in colon cancer treatment. These studies also highlighted the potential effect and mechanism of AC in the treatment of colon cancer, as well as providing insight into how to effectively use it.

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Section: Introductionmentioning

confidence: 99%

The Effect and Related Mechanism of Action of Astragalus Compatible with Curcumin against Colon Cancer Metastasis in Mice

Tang

2022

Gastroenterology Research and Practice

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“…Dextran sulphate sodium in association with AOM is used also for evaluating the contribution of inflammation to the promotion of carcinogenesis [80,81]. SPF C57BL/6 J mice and GF C56BL/6 J mice were injected with 10 mg/kg AOM i.p.…”

Section: Dextran Sulphate Sodium (Dss) Colitis and Carcinogenesis In Gf Animalsmentioning

confidence: 99%

Spontaneous and Induced Tumors in Germ-Free Animals: A General Review

et al. 2021

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Cancer, bacteria, and immunity relationships are much-debated topics in the last decade. Microbiome′s importance for metabolic and immunologic modulation of the organism adaptation and responses has become progressively evident, and models to study these relationships, especially about carcinogenesis, have acquired primary importance. The availability of germ-free (GF) animals, i.e., animals born and maintained under completely sterile conditions avoiding the microbiome development offers a unique tool to investigate the role that bacteria can have in carcinogenesis and tumor development. The comparison between GF animals with the conventional (CV) counterpart with microbiome can help to evidence conditions and mechanisms directly involving bacterial activities in the modulation of carcinogenesis processes. Here, we review the literature about spontaneous cancer and cancer modeling in GF animals since the early studies, trying to offer a practical overview on the argument.

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“…Hence, we here investigated the therapeutic efficacy of an optimized nutritional intervention designed to inhibit increased aerobic glycolysis of tumor cells in the presence or absence of an EGFR-directed antibody-based therapy in a mouse model of colitis-driven CRC. Therefore, we applied the sporadic azoxymethane (AOM)/dextran sodium sulfate (DSS) triggered mouse model of colitis-driven colorectal cancer [ 29 , 30 ]. AOM is a genotoxic carcinogen that causes DNA damage and tumorigenesis, and it specifically induces the development of colorectal cancer in rodents [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Colorectal Cancer Progression Is Potently Reduced by a Glucose-Free, High-Protein Diet: Comparison to Anti-EGFR Therapy

Skibbe

Brethack

Sünderhauf

et al. 2021

Cancers

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To enable rapid proliferation, colorectal tumor cells up-regulate epidermal growth factor receptor (EGFR) signaling and aerobic glycolysis, resulting in substantial lactate release into the tumor microenvironment and impaired anti-tumor immune responses. We hypothesized that a nutritional intervention designed to reduce aerobic glycolysis may boost the EGFR-directed antibody (Ab)-based therapy of pre-existing colitis-driven colorectal carcinoma (CRC). CRC development was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) administration to C57BL/6 mice. AOM/DSS-treated mice were fed a glucose-free, high-protein diet (GFHPD) or an isoenergetic control diet (CD) in the presence or absence of an i.p. injection of an anti-EGFR mIgG2a or respective controls. AOM/DSS-treated mice on a GFHPD displayed a reduced systemic glucose metabolism associated with reduced oxidative phosphorylation (OXPHOS) complex IV expression and diminished tumor loads. Comparable but not additive to an anti-EGFR-Ab therapy, the GFHPD was accompanied by enhanced tumoral goblet cell differentiation and decreased colonic PD-L1 and splenic CD3ε, as well as PD-1 immune checkpoint expression. In vitro, glucose-free, high-amino acid culture conditions reduced proliferation but improved goblet cell differentiation of murine and human CRC cell lines MC-38 and HT29-MTX in combination with down-regulation of PD-L1 expression. We here found GFHPD to systemically dampen glycolysis activity, thereby reducing CRC progression with a similar efficacy to EGFR-directed antibody therapy.

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Inducible mouse models of colon cancer for the analysis of sporadic and inflammation-driven tumor progression and lymph node metastasis

Cited by 52 publications

References 61 publications

The Effect and Related Mechanism of Action of Astragalus Compatible with Curcumin against Colon Cancer Metastasis in Mice

The Effect and Related Mechanism of Action of Astragalus Compatible with Curcumin against Colon Cancer Metastasis in Mice

Spontaneous and Induced Tumors in Germ-Free Animals: A General Review

Colorectal Cancer Progression Is Potently Reduced by a Glucose-Free, High-Protein Diet: Comparison to Anti-EGFR Therapy

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