Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer

Autores
Kimura, Takahito; Kruhlak, Michael; Li, Zhao; Hwang, Eunmi; Fozzatti, Laura; Cheng Sheue Yann
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Anaplastic thyroid cancer (ATC) is a lethal endocrine malignancy. It has been shown that tumor-associated macrophages (TAMs) contribute to the aggressiveness of ATC. However, stimulatory factors that could facilitate the induction and infiltration of TAMs in the ATC tumor microenvironment (TME) are not fully elucidated. In this study, we used a human leukemia monocytic cell line (THP-1) to study the differentiation of THP-1 into M2-like macrophages (M2) by conditioned media (CM) derived from each of the three human ATC cells: 8505C, THJ-11T (11T), and THJ-16T (16T). The capacity of CM to induce M2 was in the order of 16T>8505C>11T cells as determined by the expression of M2 markers (CD163, CD204, and CCL13). Cytokine arrays and ELISA assays revealed five commonly enriched cytokines (IL-6, IL-8, MCP-1, TIMP-1, and TGF-β1) in the CM derived from each of the three ATC cells. These cytokines, individually, had weak activity, but together, they mimicked full CM activity in the induction of M2. Further, they collaboratively activated STAT3, ERK, and PI3K-AKT signaling to facilitate the induction of M2 as found in CM. Importantly, we found that the CM-induced M2 could secrete soluble growth factors to promote ATC cell proliferation as evidenced by the increased Ki-67, cMYC, and cyclin D1 protein levels. Our studies identified the major stimulatory cytokines which acted collaboratively to induce M2 in the TME. Importantly, the present studies indicate that when using inhibitors to target TAMs, combination therapies would be required for effective treatment of ATC.
Fil: Kimura, Takahito. National Institutes of Health; Estados Unidos
Fil: Kruhlak, Michael. National Institutes of Health; Estados Unidos
Fil: Li, Zhao. National Institutes of Health; Estados Unidos
Fil: Hwang, Eunmi. National Institutes of Health; Estados Unidos
Fil: Fozzatti, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cheng Sheue Yann. National Institutes of Health; Estados Unidos
Materia
Cytokines
Macrophages
Anaplastic thyroid cancer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/265113
Acceder
id CONICETDig_ac100d3a52ec19b527f847d191260850
oai_identifier_str oai:ri.conicet.gov.ar:11336/265113
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancerKimura, TakahitoKruhlak, MichaelLi, ZhaoHwang, EunmiFozzatti, LauraCheng Sheue YannCytokinesMacrophagesAnaplastic thyroid cancerhttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Anaplastic thyroid cancer (ATC) is a lethal endocrine malignancy. It has been shown that tumor-associated macrophages (TAMs) contribute to the aggressiveness of ATC. However, stimulatory factors that could facilitate the induction and infiltration of TAMs in the ATC tumor microenvironment (TME) are not fully elucidated. In this study, we used a human leukemia monocytic cell line (THP-1) to study the differentiation of THP-1 into M2-like macrophages (M2) by conditioned media (CM) derived from each of the three human ATC cells: 8505C, THJ-11T (11T), and THJ-16T (16T). The capacity of CM to induce M2 was in the order of 16T>8505C>11T cells as determined by the expression of M2 markers (CD163, CD204, and CCL13). Cytokine arrays and ELISA assays revealed five commonly enriched cytokines (IL-6, IL-8, MCP-1, TIMP-1, and TGF-β1) in the CM derived from each of the three ATC cells. These cytokines, individually, had weak activity, but together, they mimicked full CM activity in the induction of M2. Further, they collaboratively activated STAT3, ERK, and PI3K-AKT signaling to facilitate the induction of M2 as found in CM. Importantly, we found that the CM-induced M2 could secrete soluble growth factors to promote ATC cell proliferation as evidenced by the increased Ki-67, cMYC, and cyclin D1 protein levels. Our studies identified the major stimulatory cytokines which acted collaboratively to induce M2 in the TME. Importantly, the present studies indicate that when using inhibitors to target TAMs, combination therapies would be required for effective treatment of ATC.Fil: Kimura, Takahito. National Institutes of Health; Estados UnidosFil: Kruhlak, Michael. National Institutes of Health; Estados UnidosFil: Li, Zhao. National Institutes of Health; Estados UnidosFil: Hwang, Eunmi. National Institutes of Health; Estados UnidosFil: Fozzatti, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cheng Sheue Yann. National Institutes of Health; Estados UnidoseCentury Publishing2024-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/265113Kimura, Takahito; Kruhlak, Michael ; Li, Zhao; Hwang, Eunmi ; Fozzatti, Laura; et al.; Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer; eCentury Publishing; American Journal of Cancer Research; 14; 12; 12-2024; 5812-58252156-6976CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.62347/QUWQ3794info:eu-repo/semantics/altIdentifier/url/https://e-century.us/files/ajcr/14/12/ajcr0161725.pdfinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:47:01Zoai:ri.conicet.gov.ar:11336/265113instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:47:01.938CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer
title Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer
spellingShingle Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer
Kimura, Takahito
Cytokines
Macrophages
Anaplastic thyroid cancer
title_short Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer
title_full Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer
title_fullStr Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer
title_full_unstemmed Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer
title_sort Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer
dc.creator.none.fl_str_mv Kimura, Takahito
Kruhlak, Michael
Li, Zhao
Hwang, Eunmi
Fozzatti, Laura
Cheng Sheue Yann
author Kimura, Takahito
author_facet Kimura, Takahito
Kruhlak, Michael
Li, Zhao
Hwang, Eunmi
Fozzatti, Laura
Cheng Sheue Yann
author_role author
author2 Kruhlak, Michael
Li, Zhao
Hwang, Eunmi
Fozzatti, Laura
Cheng Sheue Yann
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cytokines
Macrophages
Anaplastic thyroid cancer
topic Cytokines
Macrophages
Anaplastic thyroid cancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Anaplastic thyroid cancer (ATC) is a lethal endocrine malignancy. It has been shown that tumor-associated macrophages (TAMs) contribute to the aggressiveness of ATC. However, stimulatory factors that could facilitate the induction and infiltration of TAMs in the ATC tumor microenvironment (TME) are not fully elucidated. In this study, we used a human leukemia monocytic cell line (THP-1) to study the differentiation of THP-1 into M2-like macrophages (M2) by conditioned media (CM) derived from each of the three human ATC cells: 8505C, THJ-11T (11T), and THJ-16T (16T). The capacity of CM to induce M2 was in the order of 16T>8505C>11T cells as determined by the expression of M2 markers (CD163, CD204, and CCL13). Cytokine arrays and ELISA assays revealed five commonly enriched cytokines (IL-6, IL-8, MCP-1, TIMP-1, and TGF-β1) in the CM derived from each of the three ATC cells. These cytokines, individually, had weak activity, but together, they mimicked full CM activity in the induction of M2. Further, they collaboratively activated STAT3, ERK, and PI3K-AKT signaling to facilitate the induction of M2 as found in CM. Importantly, we found that the CM-induced M2 could secrete soluble growth factors to promote ATC cell proliferation as evidenced by the increased Ki-67, cMYC, and cyclin D1 protein levels. Our studies identified the major stimulatory cytokines which acted collaboratively to induce M2 in the TME. Importantly, the present studies indicate that when using inhibitors to target TAMs, combination therapies would be required for effective treatment of ATC.
Fil: Kimura, Takahito. National Institutes of Health; Estados Unidos
Fil: Kruhlak, Michael. National Institutes of Health; Estados Unidos
Fil: Li, Zhao. National Institutes of Health; Estados Unidos
Fil: Hwang, Eunmi. National Institutes of Health; Estados Unidos
Fil: Fozzatti, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cheng Sheue Yann. National Institutes of Health; Estados Unidos
description Anaplastic thyroid cancer (ATC) is a lethal endocrine malignancy. It has been shown that tumor-associated macrophages (TAMs) contribute to the aggressiveness of ATC. However, stimulatory factors that could facilitate the induction and infiltration of TAMs in the ATC tumor microenvironment (TME) are not fully elucidated. In this study, we used a human leukemia monocytic cell line (THP-1) to study the differentiation of THP-1 into M2-like macrophages (M2) by conditioned media (CM) derived from each of the three human ATC cells: 8505C, THJ-11T (11T), and THJ-16T (16T). The capacity of CM to induce M2 was in the order of 16T>8505C>11T cells as determined by the expression of M2 markers (CD163, CD204, and CCL13). Cytokine arrays and ELISA assays revealed five commonly enriched cytokines (IL-6, IL-8, MCP-1, TIMP-1, and TGF-β1) in the CM derived from each of the three ATC cells. These cytokines, individually, had weak activity, but together, they mimicked full CM activity in the induction of M2. Further, they collaboratively activated STAT3, ERK, and PI3K-AKT signaling to facilitate the induction of M2 as found in CM. Importantly, we found that the CM-induced M2 could secrete soluble growth factors to promote ATC cell proliferation as evidenced by the increased Ki-67, cMYC, and cyclin D1 protein levels. Our studies identified the major stimulatory cytokines which acted collaboratively to induce M2 in the TME. Importantly, the present studies indicate that when using inhibitors to target TAMs, combination therapies would be required for effective treatment of ATC.
publishDate 2024
dc.date.none.fl_str_mv 2024-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/265113
Kimura, Takahito; Kruhlak, Michael ; Li, Zhao; Hwang, Eunmi ; Fozzatti, Laura; et al.; Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer; eCentury Publishing; American Journal of Cancer Research; 14; 12; 12-2024; 5812-5825
2156-6976
CONICET Digital
CONICET
url http://hdl.handle.net/11336/265113
identifier_str_mv Kimura, Takahito; Kruhlak, Michael ; Li, Zhao; Hwang, Eunmi ; Fozzatti, Laura; et al.; Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer; eCentury Publishing; American Journal of Cancer Research; 14; 12; 12-2024; 5812-5825
2156-6976
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.62347/QUWQ3794
info:eu-repo/semantics/altIdentifier/url/https://e-century.us/files/ajcr/14/12/ajcr0161725.pdf
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv eCentury Publishing
publisher.none.fl_str_mv eCentury Publishing
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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