The regulation of pre-metastatic niche formation by neutrophils

Jadwiga Jablonska _, Stephan Lang, Ronit Vogt Sionov and Zvi Granot

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Oncotarget. 2017; 8:112132-112144. https://doi.org/10.18632/oncotarget.22792

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Jadwiga Jablonska1, Stephan Lang1, Ronit Vogt Sionov2 and Zvi Granot2

1Translational Oncology, Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Essen, Germany

2Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel

Correspondence to:

Jadwiga Jablonska, email: [email protected]

Zvi Granot, email: [email protected]

Keywords: neutrophils; metastatic seeding; pre-metastatic niche; neutrophil polarization in tumor context

Received: July 06, 2017     Accepted: November 14, 2017     Published: November 30, 2017


Metastasis is a multistep process requiring tumor cell detachment from the primary tumor and migration to target organs through the lymphatic or blood circulatory systems. Specific organs are predisposed to metastases in certain cancers and the formation of supportive metastatic microenvironment determines tumor cell homing. Such an environment is provided by a pre-metastatic niche that is formed through the recruitment of bone marrow-derived myeloid cells, however the mechanisms of its formation are not fully understood. Recent evidence suggests that the primary tumor itself modulates the environment of secondary organs prior to tumor cell dissemination. The contribution of neutrophils to the formation of the pre-metastatic niche is getting growing attention. Obviously, neutrophils can affect the development of metastasis in two contradicting ways, by either stimulation or inhibition of this process, depending on the activation status. Pro-tumor neutrophils actively support metastasis formation by different mechanisms, including the formation of pre-metastatic niche, tumor cell attraction, and the direct support of tumor cell proliferation. Moreover, suppressive neutrophils, which are the granulocytic arm of MDSC, promote tumor progression by dampening anti-tumor T cell immunity. On the other hand, anti-tumor neutrophils can inhibit metastasis formation by the cytotoxicity towards tumor cells in the circulation or at the pre-metastatic site, and even via stimulation of T cell proliferation. Apparently, the regulation of the pro- or anti-tumor neutrophil properties has significant implications on metastatic spread in the host. Here we provide an up to date overview of the different roles neutrophils play in regulating the metastatic processes.

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