TY - JOUR
T1 - Detection of CD39 and a Highly Glycosylated Isoform of Soluble CD73 in the Plasma of Patients with Cervical Cancer
T2 - Correlation with Disease Progression
AU - Muñóz-Godínez, Ricardo
AU - De Lourdes Mora-García, María
AU - Weiss-Steider, Benny
AU - Montesinos-Montesinos, Juan José
AU - Del Carmen Aguilar-Lemarroy, Adriana
AU - García-Rocha, Rosario
AU - Hernández-Montes, Jorge
AU - Azucena Don-López, Christian
AU - Ávila-Ibarra, Luis Roberto
AU - Torres-Pineda, Daniela Berenice
AU - Molina-Castillo, Gabriela
AU - Chacón-Salinas, Rommel
AU - Vallejo-Castillo, Luis
AU - Pérez-Tapia, Sonia Mayra
AU - Monroy-García, Alberto
N1 - Publisher Copyright:
© 2020 Ricardo Muñóz-Godínez et al.
PY - 2020
Y1 - 2020
N2 - Persistent infection with high-risk human papillomavirus (HR-HPV) is the main factor in the development of cervical cancer (CC). The presence of immunosuppressive factors plays an important role in the development of this type of cancer. To determine whether CD39 and CD73, which participate in the production of immunosuppressive adenosine (Ado), are involved in the progression of CC, we compared the concentrations and hydrolytic activity of these ectonucleotidases in platelet-free plasma (PFP) samples between patients with low-grade squamous intraepithelial lesions (LSILs) (n=18), high-grade squamous intraepithelial lesions (HSILs) (n=12), and CC (n=19) and normal donors (NDs) (n=15). The concentrations of CD39 and CD73 in PFP increased with disease progression (r=0.5929, p<0.001). The PFP of patients with HSILs or CC showed the highest concentrations of CD39 (2.3 and 2.2 times that of the NDs, respectively) and CD73 (1.7 and 2.68 times that of the NDs, respectively), which were associated with a high capacity to generate Ado from the hydrolysis of adenosine diphosphate (ADP) and adenosine monophosphate (AMP). The addition of POM-1 and APCP, specific inhibitors of CD39 and CD73, respectively, inhibited the ADPase and AMPase activity of PFP by more than 90%. A high level of the 90 kD isoform of CD73 was detected in the PFP of patients with HSILs or CC. Digestion with endoglycosidase H and N-glycanase generated CD73 with weights of approximately 90 kD, 85 kD, 80 kD, and 70 kD. In addition, the levels of transforming grow factor-β (TGF-β) in the PFPs of patients with LSIL, HSIL and CC positively correlated with those of CD39 (r=0.4432, p<0.001) and CD73 (r=0.5786, p<0.001). These results suggest that persistent infection by HR-HPV and the concomitant production of TGF-β promote the expression of CD39 and CD73 to favor CC progression through Ado generation.
AB - Persistent infection with high-risk human papillomavirus (HR-HPV) is the main factor in the development of cervical cancer (CC). The presence of immunosuppressive factors plays an important role in the development of this type of cancer. To determine whether CD39 and CD73, which participate in the production of immunosuppressive adenosine (Ado), are involved in the progression of CC, we compared the concentrations and hydrolytic activity of these ectonucleotidases in platelet-free plasma (PFP) samples between patients with low-grade squamous intraepithelial lesions (LSILs) (n=18), high-grade squamous intraepithelial lesions (HSILs) (n=12), and CC (n=19) and normal donors (NDs) (n=15). The concentrations of CD39 and CD73 in PFP increased with disease progression (r=0.5929, p<0.001). The PFP of patients with HSILs or CC showed the highest concentrations of CD39 (2.3 and 2.2 times that of the NDs, respectively) and CD73 (1.7 and 2.68 times that of the NDs, respectively), which were associated with a high capacity to generate Ado from the hydrolysis of adenosine diphosphate (ADP) and adenosine monophosphate (AMP). The addition of POM-1 and APCP, specific inhibitors of CD39 and CD73, respectively, inhibited the ADPase and AMPase activity of PFP by more than 90%. A high level of the 90 kD isoform of CD73 was detected in the PFP of patients with HSILs or CC. Digestion with endoglycosidase H and N-glycanase generated CD73 with weights of approximately 90 kD, 85 kD, 80 kD, and 70 kD. In addition, the levels of transforming grow factor-β (TGF-β) in the PFPs of patients with LSIL, HSIL and CC positively correlated with those of CD39 (r=0.4432, p<0.001) and CD73 (r=0.5786, p<0.001). These results suggest that persistent infection by HR-HPV and the concomitant production of TGF-β promote the expression of CD39 and CD73 to favor CC progression through Ado generation.
UR - http://www.scopus.com/inward/record.url?scp=85098092036&partnerID=8YFLogxK
U2 - 10.1155/2020/1678780
DO - 10.1155/2020/1678780
M3 - Artículo
C2 - 33488292
AN - SCOPUS:85098092036
SN - 0962-9351
VL - 2020
JO - Mediators of Inflammation
JF - Mediators of Inflammation
M1 - 1678780
ER -