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

First Author  Borriello L Year  2022
Journal  Nat Commun Volume  13
Issue  1 Pages  626
PubMed ID  35110548 Mgi Jnum  J:320239
Mgi Id  MGI:6870158 Doi  10.1038/s41467-022-28076-3
Citation  Borriello L, et al. (2022) Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells. Nat Commun 13(1):626
abstractText  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.
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