title: 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.
  
  
  
  We find that patients with postpartum breast cancer are at elevated risk for liver metastasis. We identify a previously unrecognized biology, namely weaning-induced liver involution, that establishes a prometastatic microenvironment, and which may account in part for the poor prognosis of patients with postpartum breast cancer. Cancer Discov; 7(2); 177-87. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 115.
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, Oregon.
authors.forename: Erica T
authors.initials: ET
authors.lastname: Goddard
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, Colorado.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Hill
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, Colorado.
authors.forename: Travis
authors.initials: T
authors.lastname: Nemkov
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, Colorado.
authors.forename: Angelo
authors.initials: A
authors.lastname: D'Alessandro
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, Colorado.
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Hansen
authors.affiliation: Department of Surgery, Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, California.
authors.forename: Ori
authors.initials: O
authors.lastname: Maller
authors.affiliation: Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Solange
authors.initials: S
authors.lastname: Mongoue-Tchokote
authors.affiliation: Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.|School of Public Health, Oregon Health & Science University, Portland, Oregon.
authors.forename: Motomi
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Ann H
authors.initials: AH
authors.lastname: Partridge
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. schedin@ohsu.edu virginia.borges@ucdenver.edu.|University of Colorado Cancer Center, Aurora, Colorado.|Young Women's Breast Cancer Translational Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Virginia F
authors.initials: VF
authors.lastname: Borges
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, Oregon. schedin@ohsu.edu virginia.borges@ucdenver.edu.|Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.|Young Women's Breast Cancer Translational Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Pepper
authors.initials: P
authors.lastname: Schedin
mesh_terms: D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000473:pathology* / Q000556:secondary*; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D049590:Postpartum Period; D051381:Rats; D059016:Tumor Microenvironment; D014886:Weaning; D055815:Young Adult