The Rodent Liver Undergoes Weaning-Induced Involution and Supports Breast Cancer Metastasis
Abstract
Patients with postpartum breast cancer are at increased risk for metastasis compared with age-matched nulliparous or pregnant patients. Here, we address whether circulating tumor cells have a metastatic advantage in the postpartum host and find the postlactation rodent liver preferentially supports metastasis. Upon weaning, we observed liver weight loss, hepatocyte apoptosis, extracellular matrix remodeling including deposition of collagen and tenascin-C, and myeloid cell influx, data consistent with weaning-induced liver involution and establishment of a prometastatic microenvironment. Using intracardiac and intraportal metastasis models, we observed increased liver metastasis in post-weaning BALB/c mice compared with nulliparous controls. Human relevance is suggested by a ∼3-fold increase in liver metastasis in patients with postpartum breast cancer (n = 564) and by liver-specific tropism (n = 117). In sum, our data reveal a previously unknown biology of the rodent liver, weaning-induced liver involution, which may provide insight into the increased liver metastasis and poor prognosis of women diagnosed with postpartum breast cancer.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 01, 2017
- Source ID
- 10.1158/2159-8290.cd-16-0822
Entities
People
- Angelo D'Alessandro
- Ann Partridge
- Erica T Goddard
- Kirk C Hansen
- Motomi Mori
- Ori Maller
- Pepper J Schedin
- Ryan C Hill
- Solange Mongoue-tchokote
- Travis Nemkov
- Virginia F Borges
Organizations
- Dana–Farber Cancer Institute
- National Institutes of Health
- Oregon Health & Science University
- United States Department of Defense
- University of California, San Francisco
- University of Colorado
- University of Colorado Denver