Pre-metastatic Niche Formation by Neutrophils in Different Organs

Metastasis is a multistep process requiring tumor cell detachment from the primary tumor and migration to secondary target organs through the lymphatic or blood circulatory systems. In certain cancers, specific organs are predisposed to metastases. Metastatic homing to distant organs is orchestrated by the formation of supportive metastatic microenvironment in such organs, called pre-metastatic niche. Formation of pre-metastatic niche depends on the primary tumor-mediated recruitment of bone marrow-derived myeloid cells, including neutrophils. The contribution of neutrophils to the formation of the pre-metastatic niche is recently getting growing attention. Of note, these cells can either stimulate or inhibit metastatic seeding, depending on the activation of these cells. Here, we concentrate on pro-metastatic functions of neutrophils and the mechanisms involved in this process. Pro-tumor neutrophils support the formation of pre-metastatic niche, attract tumor cells, and directly stimulate proliferation of these cells. Moreover, immunosuppressive neutrophils, also called granulocytic MDSC, promote metastatic progression by the inhibition of antitumor T-cells. Altogether, neutrophil pro-tumor properties significantly affect metastatic spread in the host. Here, we provide an up-to-date overview of roles neutrophils play in the regulation of metastatic processes in different organs.