RESUMEN

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-ß1, 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-ß1 in CeCa tumor cells. Blockade of A2AR and A2BR with the specific antagonists, ZM241385 and MRS1754, respectively, strongly reversed the production of TGF-ß1. TGF-ß1 produced by CeCa cells was necessary to maintain CD73 expression because the addition of anti-TGF-ß neutralizing antibodies or the inhibition of TGF-ßRI 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-ß1 and Ado as well as the autocrine activity of TGF-ß1 and expression of CD73.

Asunto(s)

5'-Nucleotidasa/metabolismo , Adenosina/metabolismo , Comunicación Autocrina/fisiología , Factor de Crecimiento Transformador beta1/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Acetamidas/farmacología , Antagonistas del Receptor de Adenosina A2/farmacología , Línea Celular Tumoral , Femenino , Proteínas Ligadas a GPI/metabolismo , Células HeLa , Humanos , Terapia de Inmunosupresión/métodos , Purinas/farmacología , Receptor de Adenosina A2A/metabolismo , Receptor de Adenosina A2B/metabolismo , Triazinas/farmacología , Triazoles/farmacología , Microambiente Tumoral/efectos de los fármacos , Neoplasias del Cuello Uterino/tratamiento farmacológico