Novel Postpartum Liver Biology Has Implications for Breast Cancer Liver Metastasis
Abstract
Women diagnosed with breast cancer within 10 years of a completed pregnancy are 2 tilde3x more likely to develop liver metastases than never-pregnant (nulliparous) patients, even after controlling for prognostic variables. This finding suggests a unique biology in the postpartum liver, a putative pre-metastatic niche, which makes postpartum patients more susceptible to liver metastases. Here we tackle the problem of defining the liver-breast cancer tumor cell niche in models of postpartum breast cancer and explore relevance to women, laying the foundation for rational drug design to treat metastatic BrCa to the liver. In rodent models, we previously reported increased liver size, hepatocyte proliferation, and anabolic metabolism during pregnancy and lactation. Within one week post-weaning, the rodent liver returned to its pre-pregnant size via a coordinated cell death and tissue remodeling process we call liver involution. To explore a potential relationship between liver involution and liver metastasis, we utilized an immune competent murine model of postpartum breast cancer. In this model, liver metastases are induced by portal vein injection of mammary tumor cells into nulliparous or involution hosts. Using two different mammary tumor cell lines, we find that the process of involution supports overt liver metastasis. To investigate if increased metastatic burden in the involuting liver is due to increased tumor cell seeding, the number of tumor cells that extravasated into the liver parenchyma was evaluated over time. Seeding was not enhanced in involution hosts. Further, in the first 3 days following injection, tumor cells were more likely to form small clusters in nulliparous hosts yet remain as single, elongated tumor cells in the involution hosts. Time-course experiments show the metastatic advantage in the postpartum host emerges tilde2 weeks after tumor cell injection.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2020
- Accession Number
- AD1110066
Entities
People
- Pepper J Schedin
Organizations
- Oregon Health & Science University