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

Cancer Signaling and Microenvironment (CSM)

Research output: Contribution to journal › Article › peer-review

64 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
Article number	626
Pages (from-to)	626
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-28076-3
State	Published - Jan 2 2022

Keywords

Animals
Breast Neoplasms/genetics
Cell Line, Tumor
Female
Humans
Mice
Mice, Inbred C57BL
Neoplasms, Experimental
Neoplastic Stem Cells
Phenotype
Tumor Microenvironment/physiology
Tumor-Associated Macrophages/physiology

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10.1038/s41467-022-28076-3

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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), 626. Article 626. https://doi.org/10.1038/s41467-022-28076-3

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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.",

keywords = "Animals, Breast Neoplasms/genetics, Cell Line, Tumor, Female, Humans, Mice, Mice, Inbred C57BL, Neoplasms, Experimental, Neoplastic Stem Cells, Phenotype, Tumor Microenvironment/physiology, Tumor-Associated Macrophages/physiology",

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 = jan,

day = "2",

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

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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, pp. 626. https://doi.org/10.1038/s41467-022-28076-3

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 - 2022/1/2

Y1 - 2022/1/2

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.

KW - Animals

KW - Breast Neoplasms/genetics

KW - Cell Line, Tumor

KW - Female

KW - Humans

KW - Mice

KW - Mice, Inbred C57BL

KW - Neoplasms, Experimental

KW - Neoplastic Stem Cells

KW - Phenotype

KW - Tumor Microenvironment/physiology

KW - Tumor-Associated Macrophages/physiology

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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

SP - 626

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

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