Zebrafish Intestinal Cancer Models

Colorectal cancer (CRC) accounts for 9% of the global cancer incidence and is one of the most common cancers in the world. Colorectal cancer includes five stages of development: abnormal lesions, small adenomas/adenomatous polyps, large adenomas, adenocarcinomas, and invasion/metastasis. Although the five-year survival rate for localized colorectal cancer is >90%, most patients with colorectal cancer are asymptomatic and thus only 40% of cases are detected at this stage. In the metastatic stage, the survival rate of colorectal cancer drops to 8-12%.

The zebrafish is an emerging model for studying tumors and tumor-organ interactions because of its many advantages. First, they are a vertebrate with highly conserved anatomical structures and homologous organs to higher vertebrates, including humans. Furthermore, most signaling pathways that control cell proliferation, apoptosis, differentiation, and motility are highly conserved between humans and zebrafish at the molecular level. The high degree of homology and the presence of oncogenes and tumor suppressor genes suggest that the oncogenic mechanisms are also highly conserved between zebrafish and higher vertebrates. Zebrafish are an ideal platform to study the molecular mechanisms of human diseases, including intestinal diseases and tumors, due to their easy and economical maintenance, high fecundity, and short generation time.

Fig. 1 Roles of zebrafish intestinal disorder and tumor models in present and future research.

Our Zebrafish Intestinal Cancer Models

Based on years of zebrafish research, Creative Biogene has successfully established a mature zebrafish intestinal tumor model. Systemic inflammation, liver enlargement, growth defects, and organ death were observed on this model, and even intestinal tumor-induced inflammation was observed in the liver of live larvae. We were able to examine gene expression and metabolism in intestinal tumors and distant livers by whole-organism transcriptome profiling.

We provide a transgenic zebrafish model of intestinal tumors that allows the assessment of key hallmarks of cancer, such as metastatic and angiogenic potential. Although the pharmacodynamics of drugs in zebrafish may differ from mammals, we have tested many compounds to demonstrate that this model can prevent disease in a similar manner. Our zebrafish gut model can provide sufficient resolution to reveal functional heterogeneity across and within tumors, including differential responses to treatments, which may be useful for studying tumor-organ crosstalk at the whole organism level.

Gene Name	System or Mutation Site	Phenotypes
mpc1	Knock down of mpc1	Failed intestinal differentiation
apc	Stop codon in the MCR	Liver and intestine tumors
apc+DMBA	Stop codon in the MCR	Intestinal adenomas
tp53M214	Point mutations in the DBM	Peripheral nerve sheath tumors, intestinal hyperplasia and adenocarcinoma
K-RASG12D	HSP-inducible Cre/Lox	Rhabdomyosarcomas, myeloproliferative disorder and Intestinal hyperplasia
cagA	B-actin-constitutive expression	Intestinal hyperplasia, dysplasia and mucosal fold fusion
cagA	FABP2-constitutive expression	Intestinal hyperplasia, dysplasia and mucosal fold fusion
cagA+tp53M214	FABP2-constitutive expression	Intestinal hyperplasia, adenocarcinoma and small cell carcinoma

Advantages

• Easy observation of tumorigenesis and tumor-induced phenotypes in live animals
• Multiple induction models
• Mass mutagenesis
• High-throughput gene/drug screening

Creative Biogene is dedicated to providing new insights into the pathogenesis of gastrointestinal diseases and helping to advance the evaluation of novel antineoplastic drugs. If you would like to learn more about zebrafish models, please feel free to contact us.

References

1. Lu JW, et al. Innovative Disease Model: Zebrafish as an In Vivo Platform for Intestinal Disorder and Tumors.; Biomedicines. 2017, 5(4):58.
2. Enya S, et al. A novel zebrafish intestinal tumor model reveals a role for cyp7a1-dependent tumor-liver crosstalk in causing adverse effects on the host.; Dis Model Mech. 2018, 11(8):dmm032383.
3. Lu JW, et al. Inducible Intestine-Specific Expression of kras^V12 Triggers Intestinal Tumorigenesis In Transgenic Zebrafish. Neoplasia. 2018, 20(12):1187-1197.

For research use only. Not intended for any clinical use.