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Models matter in metastasis

A xenograft is a transplant that occurs between two different species. A healthy immune system will predictably reject such inter-species transplants, necessitating the use of immunodeficient animals. The athymic nude mouse, an early model developed in the 1960s, remains a staple among researchers studying human cancers in animal models. However, more recently developed models with even greater immune impairments may offer improved tumor acceptance and growth. An increasingly popular example is the NSG model, a NOD-SCID mouse with deleted IL2γ receptors.

Credit: Ted Spiegel/Getty

Although immunodeficient mice will bear transplanted tumors, recapitulating metastasis is trickier. In breast cancer, metastasis is predictable in humans but limited in nude mice. Some spreading will occur as expected, but metastases in the liver, bones, or the brain are generally absent, impeding research into the later—and more lethal—stages of the disease. Looking for spontaneous metastasis to the brain, Jennifer Koblinski and her colleagues turned to the NSG mouse. Their nude-to-NSG comparison can be found in PLoS One (11, e0163521; 2016).

The team tested spontaneous metastasis using three breast cancer lines xenografted into the mammary glands of the mice. The results were striking. According to Koblinski, “some of the tumor cell lines barely grow in the nude mice but exhibit significant growth in the NSG.” NSG mice also developed metastases in more organs, including the brain, and at greater rates—up to 100% for some lines. Experimental metastasis from direct intracardiac injections confirmed similar results.

Convinced this is a good model for her research, Koblinski commented, “The NSG model will allow me to look at breast cancer metastasis to the brain using a spontaneous model as well as an experimental model.” Although she agrees that the move towards immunocompetent models is important to understand the immune system's role in cancer, transgenic mice just don't exhibit the same consistent patterns of metastasis. Allograft models, in which transplants occur between the same strains of mice with normal immune systems, are promising, but there is currently only one—the 4T1 mouse mammary tumor cell line—available.

Koblinski, who leads the Cancer Mouse Models Core at the VCU Massey Cancer Center, hopes their work will encourage others to consider the NSG mouse. She notes that researchers studying other cancers at her facility are also observing differences in tumor growth and metastasis in NSG mice compared to what is reported in the literature using nude models. “We're finding that NSG mice are just better models for studying tumor growth and metastasis of various cancers, as well as for treatment studies with different drugs.”

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Neff, E. Models matter in metastasis. Lab Anim 46, 3 (2017). https://doi.org/10.1038/laban.1170

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