Immune Milieu Established by Postpartum Liver Involution Promotes Breast Cancer Liver Metastasis
Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA
Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA
Young Women’s Breast Cancer Translational Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Author to whom correspondence should be addressed.
Academic Editors: Lingzhi Wang and Qiang Jeremy Wen
Received: 28 February 2021 / Revised: 30 March 2021 / Accepted: 2 April 2021 / Published: 3 April 2021
Cancer becomes lethal when it metastasizes to secondary sites, and for breast cancer metastasis to the liver is a serious clinical problem. Liver metastasis is promoted, in part, by changes to the liver environment, resulting in the formation of a metastatic niche that supports circulating tumor cells. Understanding how the liver niche support breast cancer cells may lead to development of treatments for patients with metastatic breast cancer. Here, we report that the developmentally regulated process of weaning-induced liver involution increases liver metastasis in cancer cells with otherwise low metastatic potential. Increased metastasis associates with unique immunological properties in the involuting liver, including reduced ability to activate T cells required for tumor cell clearance. These data establish physiologic liver involution as a model to understand the liver metastatic niche and suggest future research into whether the immune milieu identified in the involuting liver could be targeted to treat metastases more generally.