Emergency Granulopoiesis and Cancer Progression

Host

Carlos Minutti, PhD, Immunoregulation Lab

Venue

Seminar room

Abstract

Metastatic relapse can occur months to years after the cancer is first diagnosed, and it relies on the reactivation of disseminated tumour cells (DTCs) that have lied dormant in secondary organs. The acquisition and maintenance of a dormancy phenotype are tightly regulated by the interaction of DTCs with their host tissue microenvironment. In the bone, which is an organ where breast cancer displays a long period of latency, several cellular components such as stromal, immune and vascular cells can actively support dormancy, but what triggers DTC reactivation is largely unknown. We here present a strategy to engineer a mouse-to-mouse extramedullary (EM) bone, which faithfully mimics endogenous bone and that can induce the acquisition of a dormancy phenotype in highly metastatic breast cancer cells. We characterised the dormant state of metastatic cells and found that they persist in an equilibrium between two distinct transcriptional states: a more abundant quiescent and less abundant proliferative state. We found that the dynamics between the two dormant states are determined by environmental factors, and that waves of emergency granulopoiesis caused by inflammatory events such as intestinal colitis, expand the proliferative pool, increasing the chance of metastatic outgrowth. We identify upregulation of HMGB2 in neutrophil progenitors during emergency granulopoiesis as one of the factors contributing to this increased chance of breast cancer bone relapses.

Biography

Ilaria has a long-standing interest in understanding the cancer cells functional heterogeneity driving their tumourigenic potential. After a PhD at the DKFZ in Heidelberg with Dr Tommasino, she began her animal studies in Prof Joerg Huelsken lab in 2004 at the ISREC, Federal University (EPFL) of Lausanne, Switzerland. During these Postdoc years she began to investigate the importance of tumour microenvironment during metastatic progression. Building on this expertise in mouse tumour models, Ilaria set up her laboratory at the Cancer Research UK London Research Institute in 2011 (now part of the Francis Crick Institute) and has since focused the scope of investigation on the interaction that cancer cells have with the surrounding tissue cells during tumorigenesis and metastatic progression. Ilaria was promoted to Principal Group Leader at the Francis Crick Institute in 2018.

Register here.
 

About CR Colloquia Series

Champalimaud Research (CR) Colloquia Series is a seminar programme organised by the Champalimaud Centre for the Unknown to promote the discussion about the most interesting and significant questions in neuroscience and physiology & cancer with appointed speakers by the CR Community.