Open AccessPotential involvement of neutrophils in human thyroid cancer
Author(s) -
Maria Rosaria Galdiero,
Gilda Varricchi,
Stefania Loffredo,
Claudio Bellevicine,
Tiziana Lansione,
Anne Lise Ferrara,
Raffaella Ian,
Sarah Di Somma,
Francesco Borriello,
Eduardo Clery,
Maria Triassi,
Giancarlo Troncone,
Gianni Marone
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0199740
Subject(s) - chemotaxis , interleukin 8 , immunology , cancer research , inflammation , chemokine , proinflammatory cytokine , tumor necrosis factor alpha , thyroid cancer , biology , respiratory burst , cancer , microbiology and biotechnology , chemistry , medicine , receptor
Background Neutrophil functions have long been regarded as limited to acute inflammation and the defense against microbes. The role(s) of neutrophils in cancer remain poorly understood. Neutrophils infiltrate tumors and are key effector cells in the orchestration of inflammatory responses. Thyroid cancer (TC) is the most recurrent endocrine malignant tumor and is responsible for 70% of deaths due to endocrine cancers. No studies are so far available on the role of neutrophils in TC. Objective Our purpose was to study the involvement of tumor-associated neutrophils in TC. Methods Highly purified human neutrophils (>99%) from healthy donors were stimulated in vitro with conditioned media derived from TC cell lines TPC1 and 8505c (TC-CMs). Neutrophil functions (e.g., chemotaxis, activation, plasticity, survival, gene expression, and protein release) were evaluated. Results TC-derived soluble factors promoted neutrophil chemotaxis and survival. Neutrophil chemotaxis toward a TC-CM was mediated, at least in part, by CXCL8/IL-8, and survival was mediated by granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition, each TC-CM induced morphological changes and activation of neutrophils (e.g., CD11b and CD66b upregulation and CD62L shedding) and modified neutrophils’ kinetic properties. Furthermore, each TC-CM induced production of reactive oxygen species, expression of proinflammatory and angiogenic mediators (CXCL8/IL-8, VEGF-A, and TNF-α), and a release of matrix metalloproteinase 9 (MMP-9). Moreover, in TC patients, tumor-associated neutrophils correlated with larger tumor size. Conclusions TC cell lines produce soluble factors able to “educate” neutrophils toward an activated functional state. These data will advance the understanding of the molecular and cellular mechanisms of innate immunity in TC.