Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression

Autores
Fozzatti, Laura; Alamino, Vanina Alejandra; Park, Sunmi; Giusiano, Lucila; Volpini, Ximena; Zhao, Li; Stempin, Cinthia; Donadio, Ana Carolina; Cheng, Sheue-yann; Pellizas, Claudia Gabriela
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Thyroid cancer is the most common endocrine malignancy. Anaplastic thyroid cancer is one of the most aggressive thyroid tumors. It is known that activation of oncogenes and/or inactivation of tumor suppressor genes in tumor cells promotes tumorigenesis. The microenvironment of the tumor also plays a key role on cancer development and progression in a variety of tumors. However, the mechanisms by which tumor-stroma crosstalk in thyroid cancer remains poorly characterized. In this study we aimed to understand how interactions between fibroblasts and anaplastic thyroid cancer cells contribute to thyroid carcinogenesis. We first characterized the phenotypic changes of human fibroblasts in vitro through co-cultures by using transwells as well as by using anaplastic thyroid cancer cells-derived conditioned media. We found that fibroblasts acquired an activated phenotype or also known as cancer-associated fibroblast phenotype after being in contact with soluble factors secreted from anaplastic thyroid cancer cells, compared to the fibroblasts in mono-cultures. All the changes were partly mediated through Src/Akt activation. Treatment with the antioxidant N-acetyl-cysteine reversed in part the metabolic phenotype of activated fibroblasts. Remarkably, conditioned media obtained from these activated fibroblasts promoted cell proliferation and invasion of follicular thyroid cancer cell line, FTC-133 cells. Thus, a reciprocal and dynamic interaction exists between tumor and stromal cells, which results in the promotion of thyroid tumorigenesis. The present studies have advanced the understanding of the molecular basis of tumor-stroma communications, enabling identification and targeting of tumor-supportive mechanisms for novel treatment modalities.
Fil: Fozzatti, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Alamino, Vanina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Park, Sunmi. National Institutes of Health; Estados Unidos
Fil: Giusiano, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Volpini, Ximena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Zhao, Li. National Institutes of Health; Estados Unidos
Fil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Donadio, Ana Carolina. 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
Fil: Pellizas, Claudia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
Fibroblasts
Thyroid cancer
IL6
ROS
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:11336/128760
Acceder
id CONICETDig_2c145dae65fc1692707910626350cb7b
oai_identifier_str oai:ri.conicet.gov.ar:11336/128760
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progressionFozzatti, LauraAlamino, Vanina AlejandraPark, SunmiGiusiano, LucilaVolpini, XimenaZhao, LiStempin, CinthiaDonadio, Ana CarolinaCheng, Sheue-yannPellizas, Claudia GabrielaFibroblastsThyroid cancerIL6ROShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Thyroid cancer is the most common endocrine malignancy. Anaplastic thyroid cancer is one of the most aggressive thyroid tumors. It is known that activation of oncogenes and/or inactivation of tumor suppressor genes in tumor cells promotes tumorigenesis. The microenvironment of the tumor also plays a key role on cancer development and progression in a variety of tumors. However, the mechanisms by which tumor-stroma crosstalk in thyroid cancer remains poorly characterized. In this study we aimed to understand how interactions between fibroblasts and anaplastic thyroid cancer cells contribute to thyroid carcinogenesis. We first characterized the phenotypic changes of human fibroblasts in vitro through co-cultures by using transwells as well as by using anaplastic thyroid cancer cells-derived conditioned media. We found that fibroblasts acquired an activated phenotype or also known as cancer-associated fibroblast phenotype after being in contact with soluble factors secreted from anaplastic thyroid cancer cells, compared to the fibroblasts in mono-cultures. All the changes were partly mediated through Src/Akt activation. Treatment with the antioxidant N-acetyl-cysteine reversed in part the metabolic phenotype of activated fibroblasts. Remarkably, conditioned media obtained from these activated fibroblasts promoted cell proliferation and invasion of follicular thyroid cancer cell line, FTC-133 cells. Thus, a reciprocal and dynamic interaction exists between tumor and stromal cells, which results in the promotion of thyroid tumorigenesis. The present studies have advanced the understanding of the molecular basis of tumor-stroma communications, enabling identification and targeting of tumor-supportive mechanisms for novel treatment modalities.Fil: Fozzatti, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Alamino, Vanina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Park, Sunmi. National Institutes of Health; Estados UnidosFil: Giusiano, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Volpini, Ximena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Zhao, Li. National Institutes of Health; Estados UnidosFil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Donadio, Ana Carolina. 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 UnidosFil: Pellizas, Claudia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaNature Publishing Group2019-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/128760Fozzatti, Laura; Alamino, Vanina Alejandra; Park, Sunmi; Giusiano, Lucila; Volpini, Ximena; et al.; Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression; Nature Publishing Group; Scientific Reports; 9; 1; 5-2019; 1-152045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-019-44361-6info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-019-44361-6info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:48Zoai:ri.conicet.gov.ar:11336/128760instacron: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 09:59:48.7CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression
title Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression
spellingShingle Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression
Fozzatti, Laura
Fibroblasts
Thyroid cancer
IL6
ROS
title_short Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression
title_full Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression
title_fullStr Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression
title_full_unstemmed Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression
title_sort Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression
dc.creator.none.fl_str_mv Fozzatti, Laura
Alamino, Vanina Alejandra
Park, Sunmi
Giusiano, Lucila
Volpini, Ximena
Zhao, Li
Stempin, Cinthia
Donadio, Ana Carolina
Cheng, Sheue-yann
Pellizas, Claudia Gabriela
author Fozzatti, Laura
author_facet Fozzatti, Laura
Alamino, Vanina Alejandra
Park, Sunmi
Giusiano, Lucila
Volpini, Ximena
Zhao, Li
Stempin, Cinthia
Donadio, Ana Carolina
Cheng, Sheue-yann
Pellizas, Claudia Gabriela
author_role author
author2 Alamino, Vanina Alejandra
Park, Sunmi
Giusiano, Lucila
Volpini, Ximena
Zhao, Li
Stempin, Cinthia
Donadio, Ana Carolina
Cheng, Sheue-yann
Pellizas, Claudia Gabriela
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Fibroblasts
Thyroid cancer
IL6
ROS
topic Fibroblasts
Thyroid cancer
IL6
ROS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Thyroid cancer is the most common endocrine malignancy. Anaplastic thyroid cancer is one of the most aggressive thyroid tumors. It is known that activation of oncogenes and/or inactivation of tumor suppressor genes in tumor cells promotes tumorigenesis. The microenvironment of the tumor also plays a key role on cancer development and progression in a variety of tumors. However, the mechanisms by which tumor-stroma crosstalk in thyroid cancer remains poorly characterized. In this study we aimed to understand how interactions between fibroblasts and anaplastic thyroid cancer cells contribute to thyroid carcinogenesis. We first characterized the phenotypic changes of human fibroblasts in vitro through co-cultures by using transwells as well as by using anaplastic thyroid cancer cells-derived conditioned media. We found that fibroblasts acquired an activated phenotype or also known as cancer-associated fibroblast phenotype after being in contact with soluble factors secreted from anaplastic thyroid cancer cells, compared to the fibroblasts in mono-cultures. All the changes were partly mediated through Src/Akt activation. Treatment with the antioxidant N-acetyl-cysteine reversed in part the metabolic phenotype of activated fibroblasts. Remarkably, conditioned media obtained from these activated fibroblasts promoted cell proliferation and invasion of follicular thyroid cancer cell line, FTC-133 cells. Thus, a reciprocal and dynamic interaction exists between tumor and stromal cells, which results in the promotion of thyroid tumorigenesis. The present studies have advanced the understanding of the molecular basis of tumor-stroma communications, enabling identification and targeting of tumor-supportive mechanisms for novel treatment modalities.
Fil: Fozzatti, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Alamino, Vanina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Park, Sunmi. National Institutes of Health; Estados Unidos
Fil: Giusiano, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Volpini, Ximena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Zhao, Li. National Institutes of Health; Estados Unidos
Fil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Donadio, Ana Carolina. 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
Fil: Pellizas, Claudia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description Thyroid cancer is the most common endocrine malignancy. Anaplastic thyroid cancer is one of the most aggressive thyroid tumors. It is known that activation of oncogenes and/or inactivation of tumor suppressor genes in tumor cells promotes tumorigenesis. The microenvironment of the tumor also plays a key role on cancer development and progression in a variety of tumors. However, the mechanisms by which tumor-stroma crosstalk in thyroid cancer remains poorly characterized. In this study we aimed to understand how interactions between fibroblasts and anaplastic thyroid cancer cells contribute to thyroid carcinogenesis. We first characterized the phenotypic changes of human fibroblasts in vitro through co-cultures by using transwells as well as by using anaplastic thyroid cancer cells-derived conditioned media. We found that fibroblasts acquired an activated phenotype or also known as cancer-associated fibroblast phenotype after being in contact with soluble factors secreted from anaplastic thyroid cancer cells, compared to the fibroblasts in mono-cultures. All the changes were partly mediated through Src/Akt activation. Treatment with the antioxidant N-acetyl-cysteine reversed in part the metabolic phenotype of activated fibroblasts. Remarkably, conditioned media obtained from these activated fibroblasts promoted cell proliferation and invasion of follicular thyroid cancer cell line, FTC-133 cells. Thus, a reciprocal and dynamic interaction exists between tumor and stromal cells, which results in the promotion of thyroid tumorigenesis. The present studies have advanced the understanding of the molecular basis of tumor-stroma communications, enabling identification and targeting of tumor-supportive mechanisms for novel treatment modalities.
publishDate 2019
dc.date.none.fl_str_mv 2019-05
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/11336/128760
Fozzatti, Laura; Alamino, Vanina Alejandra; Park, Sunmi; Giusiano, Lucila; Volpini, Ximena; et al.; Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression; Nature Publishing Group; Scientific Reports; 9; 1; 5-2019; 1-15
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/128760
identifier_str_mv Fozzatti, Laura; Alamino, Vanina Alejandra; Park, Sunmi; Giusiano, Lucila; Volpini, Ximena; et al.; Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression; Nature Publishing Group; Scientific Reports; 9; 1; 5-2019; 1-15
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-019-44361-6
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-019-44361-6
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
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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
_version_ 1842269602297413632
score 13.13397

Publicaciones similares