Cervical cancer cells produce TGF-β1 through the CD73-adenosine pathway and maintain CD73 expression through the autocrine activity of TGF-β1
| Autor: | Jorge Hernández-Montes, Rosario García-Rocha, Benny Weiss-Steider, Luis Roberto Ávila-Ibarra, Alberto Monroy-García, María del Carmen Fuentes-Castañeda, Daniela Berenice Torres-Pineda, Vianey Gutiérrez-Serrano, Christian Azucena Don-López, María de Lourdes Mora-García |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adenosine Receptor Adenosine A2A Immunology Uterine Cervical Neoplasms Adenosinergic GPI-Linked Proteins Receptor Adenosine A2B digestive system Biochemistry Transforming Growth Factor beta1 03 medical and health sciences 0302 clinical medicine Autocrine activity Cell Line Tumor Acetamides medicine Tumor Microenvironment Immunology and Allergy Humans Secretion Molecular Biology 5'-Nucleotidase Immunosuppression Therapy biology Chemistry Triazines fungi Cancer Hematology Triazoles medicine.disease Blockade Adenosine A2 Receptor Antagonists Autocrine Communication 030104 developmental biology Purines 030220 oncology & carcinogenesis biology.protein Cancer research Female Antibody medicine.drug Transforming growth factor HeLa Cells |
| Zdroj: | Cytokine. 118 |
| ISSN: | 1096-0023 |
| Popis: | In cancer, the adenosinergic pathway participates in the generation of an immunosuppressive microenvironment and in the promotion of tumor growth through the generation of adenosine (Ado). The present study analyzed the participation of Ado, generated through the functional activity of the cervical cancer (CeCa) pathway in CeCa cells, to induce the expression and secretion of TGF-β1, as well as the participation of this factor to maintain CD73 expression. Ado concentrations greater than 10 μM were necessary to induce an increase of over 50% in the production and expression of TGF-β1 in CeCa tumor cells. Blockade of A2AR and A2BR with the specific antagonists, ZM241385 and MRS1754, respectively, strongly reversed the production of TGF-β1. TGF-β1 produced by CeCa cells was necessary to maintain CD73 expression because the addition of anti-TGF-β neutralizing antibodies or the inhibition of TGF-βRI strongly reversed the expression of CD73 in the CeCa cells. These results suggested a feedback loop in CeCa cells that favors immunosuppressive activity through the production of TGF-β1 and Ado as well as the autocrine activity of TGF–β1 and expression of CD73. |
| Databáze: | OpenAIRE |
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