Estrogen receptor-positive cell line xenograft models recapitulate metastatic dissemination and endocrine response of invasive lobular breast carcinoma

作者：Nilgun Tasdemir, Laura Savariau, Julie A. Scott, Joseph D. Latoche, Kyle Biery, Zheqi Li, Emily A. Bossart, Sreeja Sreekumar, Daniel D. Brown, Sarah Wang, Rebecca Watters, Azadeh Nasrazadani, Ye Jun Qin, Ye Cao, Fangyuan Chen, Matthew J Sikora, George Tseng, Carlos A. Castro, Carolyn J Anderson, Jennifer M. Atkinson, Jagmohan Hooda, Peter C. Lucas, Nancy E. Davidson, ADRIAN V LEE, Steffi Oesterreich · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2026 · DOI：10.64898/2026.03.17.712396 · 被引用次数：1 · 研究领域：Breast Lesions and Carcinomas、Breast Cancer Treatment Studies、Cancer Cells and Metastasis

Invasive lobular breast carcinoma (ILC), the most common special histological subtype of breast cancer, is characterized by nearly universal expression of estrogen receptor alpha (ER) and unique sites of metastases, neither of which is fully recapitulated by genetically engineered mouse models. Using reporter-labeled ILC mouse xenografts, herein we used mammary fat pad, tail vein and intracardiac orthotopic growth to analyze spontaneous and experimental metastasis and gene expression. We observed ER-positive primary tumors with single-file histology and collagen deposition, and spontaneous metastasis from the mammary fat pad to bones, ovaries, and brain including the leptomeninges, thereby closely mirroring the growth and metastatic spread of human ILC. Brain metastases showed strong ER staining, confirmed by sequencing analyses which identified estrogen signaling as top activated pathway, and the lesions exhibited robust response to endocrine therapy. In summary, we report endocrine responsive mammary fat pad, tail vein and intracardiac xenografts that faithfully demonstrate unique ILC features and can serve as invaluable pre-clinical translational platforms for validating candidate ILC genetic drivers and testing novel therapeutics.