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) (), high-grade squamous intraepithelial lesions (HSILs) (), and CC () and normal donors (NDs) (). The concentrations of CD39 and CD73 in PFP increased with disease progression (, ). 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 (, ) and CD73 (, ). 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.

中文翻译：

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在宫颈癌患者血浆中检测 CD39 和可溶性 CD73 的高度糖基化同种型：与疾病进展的相关性

高危型人乳头瘤病毒 (HR-HPV) 的持续感染是宫颈癌 (CC) 发展的主要因素。免疫抑制因子的存在在此类癌症的发展中起着重要作用。为了确定参与免疫抑制性腺苷 (Ado) 产生的 CD39 和 CD73 是否参与 CC 的进展，我们比较了低血小板血浆 (PFP​​) 样本中这些外核苷酸酶的浓度和水解活性。 -级鳞状上皮内病变（LSIL）（)、高级别鳞状上皮内病变 (HSILs) (),和 CC ()和正常供体 (NDs) (）。PFP 中 CD39 和 CD73 的浓度随着疾病进展而增加（, ）。HSILs 或 CC 患者的 PFP 显示出最高浓度的 CD39（分别为 NDs 的 2.3 和 2.2 倍）和 CD73（分别为 NDs 的 1.7 和 2.68 倍），这与高生成能力相关由二磷酸腺苷 (ADP) 和单磷酸腺苷 (AMP) 水解而成。POM-1 和 APCP（分别是 CD39 和 CD73 的特异性抑制剂）的加入分别抑制了 PFP 的 ADPase 和 AMPase 活性超过 90%。在 HSIL 或 CC 患者的 PFP 中检测到高水平的 90 kD 同种型 CD73。用内切糖苷酶 H 和 N-聚糖酶消化产生重量约为 90 kD、85 kD、80 kD 和 70 kD 的 CD73。此外，转化生长因子-β（TGF- β）在 LSIL 患者的 PFP 中，HSIL 和 CC 与 CD39 呈正相关（, )和 CD73 (, ）。这些结果表明 HR-HPV 的持续感染和伴随的 TGF- β 的产生促进 CD39 和 CD73 的表达，从而有利于通过 Ado 产生的 CC 进展。