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

doi:10.1038/s41467-022-28076-3

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 journal › Article › peer-review

51 Scopus citations

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 language	English (US)
Article number	626
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-28076-3
State	Published - Dec 2022

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/s41467-022-28076-3

Cite this

Borriello, L., Coste, A., Traub, B., Sharma, V. P., Karagiannis, G. S., Lin, Y., Wang, Y., Ye, X., Duran, C. L., Chen, X., Friedman, M., Sosa, M. S., Sun, D., Dalla, E., Singh, D. K., Oktay, M. H., Aguirre-Ghiso, J. A., Condeelis, J. S., & Entenberg, D. (2022). Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells. Nature communications, 13(1), Article 626. https://doi.org/10.1038/s41467-022-28076-3

Borriello, L, Coste, A, Traub, B, Sharma, VP, Karagiannis, GS, Lin, Y, Wang, Y, Ye, X , Duran, CL, Chen, X, Friedman, M, Sosa, MS, Sun, D, Dalla, E, Singh, DK , Oktay, MH , Aguirre-Ghiso, JA , Condeelis, JS & Entenberg, D 2022, 'Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells', Nature communications, vol. 13, no. 1, 626. https://doi.org/10.1038/s41467-022-28076-3

@article{1248e935b4d1418c83d41ceb0cd59d61,

title = "Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-28076-3",

language = "English (US)",

volume = "13",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells

AU - Borriello, Lucia

AU - Coste, Anouchka

AU - Traub, Brian

AU - Sharma, Ved P.

AU - Karagiannis, George S.

AU - Lin, Yu

AU - Wang, Yarong

AU - Ye, Xianjun

AU - Duran, Camille L.

AU - Chen, Xiaoming

AU - Friedman, Madeline

AU - Sosa, Maria Soledad

AU - Sun, Dan

AU - Dalla, Erica

AU - Singh, Deepak K.

AU - Oktay, Maja H.

AU - Aguirre-Ghiso, Julio A.

AU - Condeelis, John S.

AU - Entenberg, David

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85123972738&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85123972738&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-28076-3

DO - 10.1038/s41467-022-28076-3

M3 - Article

C2 - 35110548

AN - SCOPUS:85123972738

SN - 2041-1723

VL - 13

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 626

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this