Potential involvement of neutrophils in human thyroid cancer.
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 c...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6023126?pdf=render |
| _version_ | 1819163453935321088 |
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| author | Maria Rosaria Galdiero Gilda Varricchi Stefania Loffredo Claudio Bellevicine Tiziana Lansione Anne Lise Ferrara Raffaella Iannone Sarah di Somma Francesco Borriello Eduardo Clery Maria Triassi Giancarlo Troncone Gianni Marone |
| author_facet | Maria Rosaria Galdiero Gilda Varricchi Stefania Loffredo Claudio Bellevicine Tiziana Lansione Anne Lise Ferrara Raffaella Iannone Sarah di Somma Francesco Borriello Eduardo Clery Maria Triassi Giancarlo Troncone Gianni Marone |
| author_sort | Maria Rosaria Galdiero |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T17:44:23Z |
| format | Article |
| id | doaj.art-3451eeb08b78428e91a333ea61cfb43e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T17:44:23Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3451eeb08b78428e91a333ea61cfb43e2022-12-21T18:18:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019974010.1371/journal.pone.0199740Potential involvement of neutrophils in human thyroid cancer.Maria Rosaria GaldieroGilda VarricchiStefania LoffredoClaudio BellevicineTiziana LansioneAnne Lise FerraraRaffaella IannoneSarah di SommaFrancesco BorrielloEduardo CleryMaria TriassiGiancarlo TronconeGianni MaroneBACKGROUND: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.http://europepmc.org/articles/PMC6023126?pdf=render |
| spellingShingle | Maria Rosaria Galdiero Gilda Varricchi Stefania Loffredo Claudio Bellevicine Tiziana Lansione Anne Lise Ferrara Raffaella Iannone Sarah di Somma Francesco Borriello Eduardo Clery Maria Triassi Giancarlo Troncone Gianni Marone Potential involvement of neutrophils in human thyroid cancer. PLoS ONE |
| title | Potential involvement of neutrophils in human thyroid cancer. |
| title_full | Potential involvement of neutrophils in human thyroid cancer. |
| title_fullStr | Potential involvement of neutrophils in human thyroid cancer. |
| title_full_unstemmed | Potential involvement of neutrophils in human thyroid cancer. |
| title_short | Potential involvement of neutrophils in human thyroid cancer. |
| title_sort | potential involvement of neutrophils in human thyroid cancer |
| url | http://europepmc.org/articles/PMC6023126?pdf=render |
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