Differential expression profile of CXCR3 splicing variants is associated with thyroid neoplasia. Potential role in papillary thyroid carcinoma oncogenesis?

Soledad Urra Gamboa, Martin C. Fischer, José R. Martínez, Loreto Véliz, Paulina Orellana, Antonieta Solar, Karen Bohmwald, Alexis Kalergis, Claudia Riedel, Alejandro H. Corvalán, Juan C. Roa, Rodrigo Fuentealba, C. Joaquin Cáceres, Marcelo López-Lastra, Augusto León, Nicolás Droppelmann, Hernán E. González

Resultado de la investigación: Article

4 Citas (Scopus)

Resumen

Papillary thyroid cancer (PTC) is the most prevalent endocrine neoplasia. The increased incidence of PTC in patients with thyroiditis and the frequent immune infiltrate found in PTC suggest that inflammation might be a risk factor for PTC development. The CXCR3-ligand system is involved in thyroid inflammation and CXCR3 has been found upregulated in many tumors, suggesting its pro-tumorigenic role under the inflammatory microenvironment. CXCR3 ligands (CXCL4, CXCL9, CXCL10 and CXCL11) trigger antagonistic responses partly due to the presence of two splice variants, CXCR3A and CXCR3B. Whereas CXCR3A promotes cell proliferation, CXCR3B induces apoptosis. However, the relation between CXCR3 variant expression with chronic inflammation and PTC development remains unknown. Here, we characterized the expression pattern of CXCR3 variants and their ligands in benign tumors and PTC. We found that CXCR3A and CXCL10 mRNA levels were increased in non-metastatic PTC when compared to non-neoplastic tissue. This increment was also observed in a PTC epithelial cell line (TPC-1). Although elevated protein levels of both isoforms were detected in benign and malignant tumors, the CXCR3A expression remained greater than CXCR3B and promoted proliferation in Nthy-ori-3-1 cells. In non-metastatic PTC, inflammation was conditioning for the CXCR3 ligands increased availability. Consistently, CXCL10 was strongly induced by interferon gamma in normal and tumor thyrocytes. Our results suggest that persistent inflammation upregulates CXCL10 expression favoring tumor development via enhanced CXCR3A-CXCL10 signaling. These findings may help to further understand the contribution of inflammation as a risk factor in PTC development and set the basis for potential therapeutic studies.

Idioma originalEnglish
Páginas (desde-hasta)2445-2467
Número de páginas23
PublicaciónOncotarget
Volumen9
N.º2
DOI
EstadoPublished - 1 ene 2018

Huella dactilar

Thyroid Gland
Carcinogenesis
Neoplasms
Inflammation
Ligands
Papillary Thyroid cancer
Thyroiditis
Interferon-gamma
Protein Isoforms
Up-Regulation
Cell Proliferation
Apoptosis
Cell Line
Messenger RNA
Incidence

ASJC Scopus subject areas

  • Oncology

Citar esto

Gamboa, Soledad Urra ; Fischer, Martin C. ; Martínez, José R. ; Véliz, Loreto ; Orellana, Paulina ; Solar, Antonieta ; Bohmwald, Karen ; Kalergis, Alexis ; Riedel, Claudia ; Corvalán, Alejandro H. ; Roa, Juan C. ; Fuentealba, Rodrigo ; Cáceres, C. Joaquin ; López-Lastra, Marcelo ; León, Augusto ; Droppelmann, Nicolás ; González, Hernán E. / Differential expression profile of CXCR3 splicing variants is associated with thyroid neoplasia. Potential role in papillary thyroid carcinoma oncogenesis?. En: Oncotarget. 2018 ; Vol. 9, N.º 2. pp. 2445-2467.
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title = "Differential expression profile of CXCR3 splicing variants is associated with thyroid neoplasia. Potential role in papillary thyroid carcinoma oncogenesis?",
abstract = "Papillary thyroid cancer (PTC) is the most prevalent endocrine neoplasia. The increased incidence of PTC in patients with thyroiditis and the frequent immune infiltrate found in PTC suggest that inflammation might be a risk factor for PTC development. The CXCR3-ligand system is involved in thyroid inflammation and CXCR3 has been found upregulated in many tumors, suggesting its pro-tumorigenic role under the inflammatory microenvironment. CXCR3 ligands (CXCL4, CXCL9, CXCL10 and CXCL11) trigger antagonistic responses partly due to the presence of two splice variants, CXCR3A and CXCR3B. Whereas CXCR3A promotes cell proliferation, CXCR3B induces apoptosis. However, the relation between CXCR3 variant expression with chronic inflammation and PTC development remains unknown. Here, we characterized the expression pattern of CXCR3 variants and their ligands in benign tumors and PTC. We found that CXCR3A and CXCL10 mRNA levels were increased in non-metastatic PTC when compared to non-neoplastic tissue. This increment was also observed in a PTC epithelial cell line (TPC-1). Although elevated protein levels of both isoforms were detected in benign and malignant tumors, the CXCR3A expression remained greater than CXCR3B and promoted proliferation in Nthy-ori-3-1 cells. In non-metastatic PTC, inflammation was conditioning for the CXCR3 ligands increased availability. Consistently, CXCL10 was strongly induced by interferon gamma in normal and tumor thyrocytes. Our results suggest that persistent inflammation upregulates CXCL10 expression favoring tumor development via enhanced CXCR3A-CXCL10 signaling. These findings may help to further understand the contribution of inflammation as a risk factor in PTC development and set the basis for potential therapeutic studies.",
keywords = "Chemokine receptors, CXCL10, CXCR3, Inflammation, Papillary thyroid cancer",
author = "Gamboa, {Soledad Urra} and Fischer, {Martin C.} and Mart{\'i}nez, {Jos{\'e} R.} and Loreto V{\'e}liz and Paulina Orellana and Antonieta Solar and Karen Bohmwald and Alexis Kalergis and Claudia Riedel and Corval{\'a}n, {Alejandro H.} and Roa, {Juan C.} and Rodrigo Fuentealba and C{\'a}ceres, {C. Joaquin} and Marcelo L{\'o}pez-Lastra and Augusto Le{\'o}n and Nicol{\'a}s Droppelmann and Gonz{\'a}lez, {Hern{\'a}n E.}",
year = "2018",
month = "1",
day = "1",
doi = "10.18632/oncotarget.23502",
language = "English",
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Gamboa, SU, Fischer, MC, Martínez, JR, Véliz, L, Orellana, P, Solar, A, Bohmwald, K, Kalergis, A, Riedel, C, Corvalán, AH, Roa, JC, Fuentealba, R, Cáceres, CJ, López-Lastra, M, León, A, Droppelmann, N & González, HE 2018, 'Differential expression profile of CXCR3 splicing variants is associated with thyroid neoplasia. Potential role in papillary thyroid carcinoma oncogenesis?', Oncotarget, vol. 9, n.º 2, pp. 2445-2467. https://doi.org/10.18632/oncotarget.23502

Differential expression profile of CXCR3 splicing variants is associated with thyroid neoplasia. Potential role in papillary thyroid carcinoma oncogenesis? / Gamboa, Soledad Urra; Fischer, Martin C.; Martínez, José R.; Véliz, Loreto; Orellana, Paulina; Solar, Antonieta; Bohmwald, Karen; Kalergis, Alexis; Riedel, Claudia; Corvalán, Alejandro H.; Roa, Juan C.; Fuentealba, Rodrigo; Cáceres, C. Joaquin; López-Lastra, Marcelo; León, Augusto; Droppelmann, Nicolás; González, Hernán E.

En: Oncotarget, Vol. 9, N.º 2, 01.01.2018, p. 2445-2467.

Resultado de la investigación: Article

TY - JOUR

T1 - Differential expression profile of CXCR3 splicing variants is associated with thyroid neoplasia. Potential role in papillary thyroid carcinoma oncogenesis?

AU - Gamboa, Soledad Urra

AU - Fischer, Martin C.

AU - Martínez, José R.

AU - Véliz, Loreto

AU - Orellana, Paulina

AU - Solar, Antonieta

AU - Bohmwald, Karen

AU - Kalergis, Alexis

AU - Riedel, Claudia

AU - Corvalán, Alejandro H.

AU - Roa, Juan C.

AU - Fuentealba, Rodrigo

AU - Cáceres, C. Joaquin

AU - López-Lastra, Marcelo

AU - León, Augusto

AU - Droppelmann, Nicolás

AU - González, Hernán E.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Papillary thyroid cancer (PTC) is the most prevalent endocrine neoplasia. The increased incidence of PTC in patients with thyroiditis and the frequent immune infiltrate found in PTC suggest that inflammation might be a risk factor for PTC development. The CXCR3-ligand system is involved in thyroid inflammation and CXCR3 has been found upregulated in many tumors, suggesting its pro-tumorigenic role under the inflammatory microenvironment. CXCR3 ligands (CXCL4, CXCL9, CXCL10 and CXCL11) trigger antagonistic responses partly due to the presence of two splice variants, CXCR3A and CXCR3B. Whereas CXCR3A promotes cell proliferation, CXCR3B induces apoptosis. However, the relation between CXCR3 variant expression with chronic inflammation and PTC development remains unknown. Here, we characterized the expression pattern of CXCR3 variants and their ligands in benign tumors and PTC. We found that CXCR3A and CXCL10 mRNA levels were increased in non-metastatic PTC when compared to non-neoplastic tissue. This increment was also observed in a PTC epithelial cell line (TPC-1). Although elevated protein levels of both isoforms were detected in benign and malignant tumors, the CXCR3A expression remained greater than CXCR3B and promoted proliferation in Nthy-ori-3-1 cells. In non-metastatic PTC, inflammation was conditioning for the CXCR3 ligands increased availability. Consistently, CXCL10 was strongly induced by interferon gamma in normal and tumor thyrocytes. Our results suggest that persistent inflammation upregulates CXCL10 expression favoring tumor development via enhanced CXCR3A-CXCL10 signaling. These findings may help to further understand the contribution of inflammation as a risk factor in PTC development and set the basis for potential therapeutic studies.

AB - Papillary thyroid cancer (PTC) is the most prevalent endocrine neoplasia. The increased incidence of PTC in patients with thyroiditis and the frequent immune infiltrate found in PTC suggest that inflammation might be a risk factor for PTC development. The CXCR3-ligand system is involved in thyroid inflammation and CXCR3 has been found upregulated in many tumors, suggesting its pro-tumorigenic role under the inflammatory microenvironment. CXCR3 ligands (CXCL4, CXCL9, CXCL10 and CXCL11) trigger antagonistic responses partly due to the presence of two splice variants, CXCR3A and CXCR3B. Whereas CXCR3A promotes cell proliferation, CXCR3B induces apoptosis. However, the relation between CXCR3 variant expression with chronic inflammation and PTC development remains unknown. Here, we characterized the expression pattern of CXCR3 variants and their ligands in benign tumors and PTC. We found that CXCR3A and CXCL10 mRNA levels were increased in non-metastatic PTC when compared to non-neoplastic tissue. This increment was also observed in a PTC epithelial cell line (TPC-1). Although elevated protein levels of both isoforms were detected in benign and malignant tumors, the CXCR3A expression remained greater than CXCR3B and promoted proliferation in Nthy-ori-3-1 cells. In non-metastatic PTC, inflammation was conditioning for the CXCR3 ligands increased availability. Consistently, CXCL10 was strongly induced by interferon gamma in normal and tumor thyrocytes. Our results suggest that persistent inflammation upregulates CXCL10 expression favoring tumor development via enhanced CXCR3A-CXCL10 signaling. These findings may help to further understand the contribution of inflammation as a risk factor in PTC development and set the basis for potential therapeutic studies.

KW - Chemokine receptors

KW - CXCL10

KW - CXCR3

KW - Inflammation

KW - Papillary thyroid cancer

UR - http://www.scopus.com/inward/record.url?scp=85039978868&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.23502

DO - 10.18632/oncotarget.23502

M3 - Article

AN - SCOPUS:85039978868

VL - 9

SP - 2445

EP - 2467

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 2

ER -