Abstract

Triple-negative breast cancer (TNBC) has a more aggressive phenotype and higher metastasis and recurrence rates than other breast cancer subtypes. TNBC currently lacks a transplantation model that is suitable for clinical simulations of the tumor microenvironment. Intraductal injection of tumor cells into the mammary duct could mimic the occurrence and development of breast cancer. Herein, we injected 4T1 cells into the mammary ducts of BALB/C mice to build a preclinical model of TNBC and optimized the related construction method to observe the occurrence and spontaneous metastasis of tumors. We compared the effects of different cell numbers on tumorigenesis rates, times to tumorigenesis, and metastases to determine the optimal number of cells for modelling. We demonstrated that 4T1-MIND model mice injected with 20,000 cells revealed a suitable tumor formation rate and time, thus indicating a potential treatment time window after distant metastasis. We also injected 20,000 cells directly into the breast fat pad or breast duct for parallel comparison. The results still showed that the 4T1-MIND model provides sufficient treatment time for lung metastases in mice and that it is a more reliable model for early tumor development. The 4T1-MIND model requires continuous improvement and optimization. A suitable and optimized model for translational research and studies on the microenvironment in TNBC should be developed.

Highlights

  • Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer death among women worldwide[1,2]

  • Tumors became palpable within 10 days in animals implanted with 100,000 cells, within 12 days in animals implanted with 40,000 cells, within 15 days in animals implanted with 20,000 cells, within 19 days in animals implanted with 10,000 cells, within 25 days in animals implanted with 5,000 cells, and within 29 days in animals implanted with 2,500 cells

  • We established a mouse model that is physiologically homologous to Triple-negative breast cancer (TNBC)

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Summary

Introduction

Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer death among women worldwide[1,2]. Animal models that can mimic the microenvironment of breast cancer are scarce, but many studies need such models. The lack of a model that can mimic the tumor microenvironment and demonstrate spontaneous metastasis has hampered progress in understanding breast cancer evolution and therapy. An excellent animal model of breast cancer is still needed; such a model should (1) clinically represent a certain type of breast cancer; (2) feature feasible and simple operations with wide applicability to laboratories; (3) mimic the breast cancer microenvironment and spontaneous metastasis; and (4) have an intact immune system. The purpose of this article is to describe an animal model that can mimic the tumor microenvironment, demonstrate the spontaneous metastasis of breast cancer, and maintain a complete immune system. We have generated animal models or optimized them on the basis of the original models, which is of great significance for the application of this model in breast cancer research

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