Abstract 1167: A syngeneic MIND model for triple-negative breast cancer: A novel metastatic mouse model for disease progression and therapeutic studies

Abstract

Abstract Background and Objective: In the era of targeted therapy mouse models have significantly contributed to our understanding of cancer biology. Insight into the molecular pathways has opened new avenues for cancer therapeutic strategies. Majority of the available mouse models depict a portion of the breast cancer progression cascade to be investigated. Some mimic the tumorigenesis at an early stage, some portray the later stage of metastatic process. Additionally, most of the mouse models lack the ability to depict the functional contribution of immune system during metastatic progression because very often they deal with immune-compromised mice. Hence a mouse model that can represent all the stages of breast cancer tumorigenesis and metastasis in native microenvironment in presence of immunity is exceptionally essential. This notion gave us an idea to develop a syngeneic mice model that will epitomize all the breast cancer progression stages and in very short time. Methods: A modified mouse mammary intraductal (MIND) method was adopted for this study. MVT-1 and 4T1 cells were injected into cleaved nipples of 4th inguinal mammary glands of FVB/N and BALB/c wild-type female mice, respectively. The concentration of cells was 10,000 cells/µL. The final volume did not exceed 5 µL per injection per gland. Tissues were harvested at required time points. Histopathology was confirmed by haematoxylin-eosin staining and was further confirmed by immunohistochemical markers for cell proliferation, epithelial-to-mesenchymal transition (EMT), invasion, intravasation, extravasation and metastasis. Results and Conclusions: Primary tumor had been established by the end of first week of injection and was confirmed by histopathology and whole mount analysis of 4th inguinal mammary gland. During second week after cell inoculation, cells had gone through EMT and had prepared and started invasion. Invasion was followed by intravasation and metastasis. Microscopic metastatic patches in the lungs were observed during third week and visible patches were observed during fourth week after injection. The main advantage of this model is short time span. Our model becomes more relevant as the origin of primary tumor and metastasis takes place in same animal, closely resembling biologic progression of breast cancer with the ability to depict the functional contribution of immune system during metastatic progression. A syngeneic mice model like ours can recapitulate the successive stages of breast cancer tumor progression and metastasis and could give the entire picture of metastatic process. We believe that our syngeneic mouse model will facilitate “drug-hunters” and basic science researchers towards developing improved breast cancer treatment. Citation Format: Arnab Ghosh, Sandipto Sarkar, Fariba Behbod, Snigdha Banerjee, Ossama W. Tawfik, Sushanta K. Banerjee. A syngeneic MIND model for triple-negative breast cancer: A novel metastatic mouse model for disease progression and therapeutic studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1167.