Tumor entrained neutrophils inhibit seeding in the premetastatic lung

Zvi Granot, Erik Henke, Elizabeth A. Comen, Tari A. King, Larry Norton, Robert Benezra*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

586 Scopus citations

Abstract

Primary tumors have been shown to prepare distal organs for later colonization of metastatic cells by stimulating organ-specific infiltration of bone marrow derived cells. Here we demonstrate that neutrophils accumulate in the lung prior to the arrival of metastatic cells in mouse models of breast cancer. Tumor-entrained neutrophils (TENs) inhibit metastatic seeding in the lungs by generating H2O2 and tumor secreted CCL2 is a critical mediator of optimal antimetastatic entrainment of G-CSF-stimulated neutrophils. TENs are present in the peripheral blood of breast cancer patients prior to surgical resection but not in healthy individuals. Thus, whereas tumor-secreted factors contribute to tumor progression at the primary site, they concomitantly induce a neutrophil-mediated inhibitory process at the metastatic site.

Original languageAmerican English
Pages (from-to)300-314
Number of pages15
JournalCancer Cell
Volume20
Issue number3
DOIs
StatePublished - Sep 2011
Externally publishedYes

Bibliographical note

Funding Information:
R.B. is supported by grants from the NIH and the Breast Cancer Research Foundation. We thank Dr. Edi Brogi, Dr. Juan-Manuel Schvartzman, Sho Fujisawa, Oren Litvin, and Yvette Chin for technical assistance, Dr. Eric Pamer and Dr. Lindy Barrett (MSKCC, New York) for critical reading of this manuscript and Isaac Kaplan for his assistance with image analysis.

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