Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells

Lucia Borriello, Anouchka Coste, Brian Traub, Ved P. Sharma, George S. Karagiannis, Yu Lin, Yarong Wang, Xianjun Ye, Camille L. Duran, Xiaoming Chen, Madeline Friedman, Maria Soledad Sosa, Dan Sun, Erica Dalla, Deepak K. Singh, Maja H. Oktay, Julio A. Aguirre-Ghiso, John S. Condeelis, David Entenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Metastases are initiated by disseminated tumor cells (DTCs) that colonize distant organs. Growing evidence suggests that the microenvironment of the primary tumor primes DTCs for dormant or proliferative fates. However, the manner in which this occurs remains poorly understood. Here, using the Window for High-Resolution Intravital Imaging of the Lung (WHRIL), we study the live lung longitudinally and follow the fate of individual DTCs that spontaneously disseminate from orthotopic breast tumors. We find that spontaneously DTCs have increased levels of retention, increased speed of extravasation, and greater survival after extravasation, compared to experimentally metastasized tumor cells. Detailed analysis reveals that a subset of macrophages within the primary tumor induces a pro-dissemination and pro-dormancy DTC phenotype. Our work provides insight into how specific primary tumor microenvironments prime a subpopulation of cells for expression of proteins associated with dissemination and dormancy.

Original languageEnglish (US)
Article number626
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint

Dive into the research topics of 'Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells'. Together they form a unique fingerprint.

Cite this