Abstract
Metastasis is the most common cause of mortality in breast cancer patients worldwide. To identify improved mouse models for breast cancer growth and spontaneous metastasis, we examined growth and metastasis of both estrogen receptor positive (T47D) and negative (MDA-MB-231, SUM1315, and CN34BrM) human breast cancer cells in nude and NSG mice. Both primary tumor growth and spontaneous metastases were increased in NSG mice compared to nude mice. In addition, a pattern of metastasis similar to that observed in human breast cancer patients (metastases to the lungs, liver, bones, brain, and lymph nodes) was found in NSG mice. Furthermore, there was an increase in the metastatic burden in NSG compared to nude mice that were injected with MDA-MB-231 breast cancer cells in an intracardiac experimental metastasis model. This data demonstrates that NSG mice provide a better model for studying human breast cancer metastasis compared to the current nude mouse model.
Highlights
Breast cancer has a high propensity to metastasize to the lungs, liver, bones, brain, and lymph nodes leading to patient death within 1–5 years after the first metastasis [1]
Iorns et al demonstrated that when human breast cancer cells are injected into the orthotopic site of NSG mice, the cells metastasize in distant organs without the need to resect the primary tumor [37]
We found that tumor cell engraftment, growth, and metastasis from the mammary fat pad was better in NSG mice than in nude mice for both ER+ (T47D) and ER- (CN34BrM, MDA-MB-231, and SUM1315) breast cancer cell lines
Summary
Breast cancer has a high propensity to metastasize to the lungs, liver, bones, brain, and lymph nodes leading to patient death within 1–5 years after the first metastasis [1]. Despite the widely acknowledged magnitude of breast cancer metastasis, there is still a critical gap in resolving the mechanisms of breast cancer metastasis and its organotropism. Paget’s “seed and soil” hypothesis proposed that breast cancer cells, “the seeds,” metastasize to many organs but grow only where the stroma, “the soil,” is permissive [2]. Years of accumulating evidence have revealed that the tumor-stromal interaction is essential for metastatic tumor growth as well as primary. A Better Mouse Model for Spontaneous Breast Cancer Metastasis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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