TY - JOUR
T1 - Mesenchymal Stromal Cells Derived from Normal Cervix and Cervical Cancer Tumors Increase CD73 Expression in Cervical Cancer Cells Through TGF-β1 Production
AU - Ávila-Ibarra, Luis Roberto
AU - Mora-Garcia, María De Lourdes
AU - García-Rocha, Rosario
AU - Hernández-Montes, Jorge
AU - Weiss-Steider, Benny
AU - Montesinos, Juan José
AU - Lizano Soberon, Marcela
AU - García-López, Patricia
AU - López, Christian Azucena Don
AU - Torres-Pineda, Daniela Berenice
AU - Chacón-Salinas, Rommel
AU - Vallejo-Castillo, Luis
AU - Pérez-Tapia, Sonia Mayra
AU - Monroy-Garcia, Alberto
N1 - Publisher Copyright:
© Copyright 2019, Mary Ann Liebert, Inc., publishers 2019.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Mesenchymal stromal cells (MSCs) in the tumor microenvironment (TME) participate together with tumor cells to suppress antitumor effector cells through the production of immunosuppressive factors, such as transforming growth factor-beta 1 (TGF-β1). Furthermore, TGF-β1 can induce 5′-nucleotidase (CD73) expression in various cell types; this functional activity is associated with the production of adenosine (Ado), which is an immunosuppressive nucleoside. In this study, we provide evidence that coculture of MSCs derived from cervical tumors (CeCa-MSC) with CeCa tumor cells increases CD73 expression in tumor cells and the capacity of these cells to generate Ado in a MSC ratio-dependent manner. Interestingly, the increase in CD73 in the CeCa cell membrane corresponded to an increase in the TGF-β1 expression level in the tumor cells and the TGF-β1 content in the supernatants of the CeCa/CeCa-MSC cocultures. The addition of anti-hTGF-β neutralizing antibodies strongly reversed CD73 expression in the tumor cells. This phenomenon was not exclusive to CeCa-MSCs; coculture of MSCs derived from the normal cervix with CeCa cells produced similar results. These results suggest that the interaction of MSCs with CeCa tumor cells in the TME may condition higher TGF-β1 production to maintain an immunosuppressive status not only through the activity of this cytokine per se but also through its ability to induce CD73 expression in tumor cells and generate an immunosuppressive microenvironment rich in Ado.
AB - Mesenchymal stromal cells (MSCs) in the tumor microenvironment (TME) participate together with tumor cells to suppress antitumor effector cells through the production of immunosuppressive factors, such as transforming growth factor-beta 1 (TGF-β1). Furthermore, TGF-β1 can induce 5′-nucleotidase (CD73) expression in various cell types; this functional activity is associated with the production of adenosine (Ado), which is an immunosuppressive nucleoside. In this study, we provide evidence that coculture of MSCs derived from cervical tumors (CeCa-MSC) with CeCa tumor cells increases CD73 expression in tumor cells and the capacity of these cells to generate Ado in a MSC ratio-dependent manner. Interestingly, the increase in CD73 in the CeCa cell membrane corresponded to an increase in the TGF-β1 expression level in the tumor cells and the TGF-β1 content in the supernatants of the CeCa/CeCa-MSC cocultures. The addition of anti-hTGF-β neutralizing antibodies strongly reversed CD73 expression in the tumor cells. This phenomenon was not exclusive to CeCa-MSCs; coculture of MSCs derived from the normal cervix with CeCa cells produced similar results. These results suggest that the interaction of MSCs with CeCa tumor cells in the TME may condition higher TGF-β1 production to maintain an immunosuppressive status not only through the activity of this cytokine per se but also through its ability to induce CD73 expression in tumor cells and generate an immunosuppressive microenvironment rich in Ado.
KW - CD73
KW - TGF-b
KW - adenosine
KW - cervical cancer
KW - mesenchymal stromal cells
UR - http://www.scopus.com/inward/record.url?scp=85063814400&partnerID=8YFLogxK
U2 - 10.1089/scd.2018.0183
DO - 10.1089/scd.2018.0183
M3 - Artículo
C2 - 30696359
AN - SCOPUS:85063814400
SN - 1547-3287
VL - 28
SP - 477
EP - 488
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 7
ER -