Tumor Microenvironment Regulates Metastasis and Metastasis Genes of Mouse MMTV-PymT Mammary Cancer Cells In Vivo

• Published in: Veterinary pathology Vol. 51; no. 4; pp. 868 - 881
• Main Authors: Werbeck, J. L., Thudi, N. K., Martin, C. K., Premanandan, C., Yu, L., Ostrowksi, M. C., Rosol, T. J.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.07.2014
• Subjects: Analysis of Variance; Animals; Cell Line, Tumor; Disease Models, Animal; Female; Gene Expression Profiling - veterinary; Gene Expression Regulation, Neoplastic - genetics; Gene Expression Regulation, Neoplastic - physiology; Genes, Neoplasm - genetics; Genes, Neoplasm - physiology; Histological Techniques - veterinary; Immunohistochemistry - veterinary; Mammary Neoplasms, Animal - pathology; Mice; Neoplasm Metastasis - genetics; Neoplasm Metastasis - physiopathology; Reverse Transcriptase Polymerase Chain Reaction - veterinary; Tumor Microenvironment - physiology; lung; ovary; metastasis; PyMT; mammary cancer; breast cancer; mammary tumor; bone
• ISSN: 0300-9858; 1544-2217
• DOI: 10.1177/0300985813505116

Metastasis is the primary cause of death in breast cancer patients, yet there are challenges to modeling this process in vivo. The goal of this study was to analyze the effects of injection site on tumor growth and metastasis and gene expression of breast cancer cells in vivo using the MMTV-PymT breast cancer model (Met-1 cells). Met-1 cells were injected into 5 sites (subcutaneous, mammary fat pad, tail vein, intracardiac, and intratibial), and tumors and metastases were monitored using bioluminescent imaging and confirmed with gross necropsy and histopathology. Met-1 tumors were analyzed based on morphology and changes in gene expression in each tissue microenvironment. There were 6 permissible sites of Met-1 tumor growth (mammary gland, subcutis, lung, adrenal gland, ovary, bone). Met-1 cells grew faster in the subcutis compared to mammary fat pad tumors (highest Ki-67 index). Morphologic differences were evident in each tumor microenvironment. Finally, 7 genes were differentially expressed in the Met-1 tumors in the 6 sites of growth or metastasis. This investigation demonstrates that breast cancer progression and metastasis are regulated by not only the tumor cells but also the experimental model and unique molecular signals from the tumor microenvironment.