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Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model

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Abstract

During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between “species-specific” mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for “species-specific” tissue metastasis to human tissues. Comprehensive analyses suggest that “species-specific” mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

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Acknowledgments

This research was supported in part by National Natural Science Foundation of China (81172502, 81302305), Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU (IRT-008), Natural Science Foundation of Jiangsu Province (BK20131027), Youth Talent Project in Jiangsu Province Hospital (FRC201308), a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and Jiangsu Province Innovation Project for Graduate Student of China (CXZZ11_0723, to MJZ).

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Authors and Affiliations

  1. Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, China

    Ming-Jie Zheng, Jue Wang, Lu Xu, Xiao-Ming Zha, Yi Zhao, Li-Jun Ling & Shui Wang

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  1. Ming-Jie Zheng
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  2. Jue Wang
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  3. Lu Xu
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  4. Xiao-Ming Zha
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  5. Yi Zhao
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  6. Li-Jun Ling
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  7. Shui Wang
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Corresponding author

Correspondence to Shui Wang.

Additional information

Ming-Jie Zheng and Jue Wang have contributed equally to this work.

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Zheng, MJ., Wang, J., Xu, L. et al. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model. Med Oncol 32, 8 (2015). https://doi.org/10.1007/s12032-014-0427-4

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  • DOI: https://doi.org/10.1007/s12032-014-0427-4

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