Purinergic signaling and tumor microenvironment in cervical Cancer

Pfaffenzeller, Marta Schmidt; Franciosi, Maria Luiza Mukai; Cardoso, Andréia Machado

doi:10.1007/s11302-020-09693-3

Cited by 26 publications

(17 citation statements)

References 116 publications

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“…Therefore, the results obtained in this study suggest that the production of TGF- β associated with persistent infection by HR-HPV may be an important factor inducing and maintaining the expression of the CD39 and CD73 ectonucleotidases during the development of CC. Considering the important role of the adenosinergic pathway in the suppression of the antitumor immune response through Ado generation [ 13 ] and that the presence of high concentrations of extracellular nucleotides in the TME of CC seems to interfere with the regulation, proliferation, differentiation, and apoptosis of cancer cells of the cervix [ 49 ], the concentrations and activity of CD39 and CD73 in the plasma of patients with CC may be valuable biomarkers of disease progression and may direct the choice of clinical treatment for these patients.…”

Section: Discussionmentioning

confidence: 99%

Detection of CD39 and a Highly Glycosylated Isoform of Soluble CD73 in the Plasma of Patients with Cervical Cancer: Correlation with Disease Progression

Muñóz-Godínez

Mora‐García²,

Weiss‐Steider³

et al. 2020

Mediators of Inflammation

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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.

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Section: Discussionmentioning

confidence: 99%

Detection of CD39 and a Highly Glycosylated Isoform of Soluble CD73 in the Plasma of Patients with Cervical Cancer: Correlation with Disease Progression

Muñóz-Godínez

Mora‐García²,

Weiss‐Steider³

et al. 2020

Mediators of Inflammation

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“…This gene is one of the regulators of an inflammation in the host immune response and that has been associated with the carcinogenic process (Slattery et al, 2018). As several factors are involved in cervical cancer development, including intrinsic factors related to the inflammatory process (Pfaffenzeller et al, 2020) the up-regulation to related genes seems crucial.…”

Section: Discussionmentioning

confidence: 99%

“…The fourth most common type of cancer among the female population is cervical cancer. It has become a health problem in term of morbidity and mortality worldwide (Pfaffenzeller et al, 2020, Keinan Boker et al, 2020.…”

Section: Introductionmentioning

confidence: 99%

The anticancer molecular mechanism of Carnosol in human cervical cancer cells: An in vitro study

Hafidh

Abdulamir

2020

APJMBB

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Carnosol, a phenolic diterpene, is one of the effective anticancer agents naturally occurring in rosemary, sage, parsley, and oregano. The chemoresistance problem increased with the routinely used chemotherapy. Therefore, the efforts to find a substitute with safe and low cost have become crucial worldwide. The current study attempts to inspect the anticancer molecular mechanisms of Carnosol on modulating up- and down- regulation of multiple genetic carcinogenesis pathways. The cytotoxicity of Carnosol on Hela cells was evaluated by MTS assay. Flow cytometry was used to assess apoptosis and cell cycle arrest. The apoptotic morphological changes were obvious by dual apoptosis assay. The differential gene expression after treatment with Carnosol was investigated by qRT-PCR. Up to 80% of the treated cells with Carnosol IC50 underwent apoptosis. Apoptosis together with cell cycle arrest in G0/G1 phase were induced significantly after treatment with Carnosol IC50. Fifteen out of nineteen genes studied were found to be remarkably up- or down- regulated after treatment with Carnosol. Six up-regulated genes (EREG, FOS-2, ID2, CRYAB, DUSP5, and TICAM2) and nine down-regulated genes (FN1, KRAS2, CCNB1-1, FEN1, MCM4, MCM5, GTSE1, CXCL1, and RALA) were recorded. These genes are candidates for future research for elucidating anticancer molecular targeted therapies, cancerous signaling and cancer development pathways in cervical cancer; moreover, elucidating the role of apoptosis, inflammation, cell proliferation, and cell differentiation in the development of cervical cancer.

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“…Since its conception in the early 1970s by Professor Geoffrey Burnstock, the purinergic signaling system has been extensively studied and correlated with several immunological changes, such as those that occur during viral infection and blood clotting [ 1 , 2 ]. The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) started in December 2019 in China and already accounts for more than 2.4 million deaths worldwide by February 24 2021, according to the World Health Organization [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Possible role of purinergic signaling in COVID-19

et al. 2021

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The coronavirus disease (COVID-19), caused by SARS-CoV-2 infection, accounts for more than 2.4 million deaths worldwide, making it the main public health problem in 2020. Purinergic signaling is involved in the pathophysiology of several viral infections which makes the purinergic system a potential target of investigation in COVID-19. During viral infections, the ATP release initiates a cascade that activates purinergic receptors. This receptor activation enhances the secretion of pro-inflammatory cytokines and performs the chemotaxis of macrophages and neutrophils, generating an association between the immune and the purinergic systems. This review was designed to cover the possible functions of purinergic signaling in COVID-19, focusing on the possible role of purinergic receptors such as P2X7 which contributes to cytokine storm and inflammasome NLRP3 activation and P2Y1 that activates the blood coagulation pathway. The possible role of ectonucleotidases, such as CD39 and CD73, which have the function of dephosphorylating ATP in an immunosuppressive component, adenosine, are also covered in detail. Moreover, therapeutic combination or association possibilities targeting purinergic system components are also suggested as a possible useful tool to be tested in future researches, aiming to unveil a novel option to treat COVID-19 patients.

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Purinergic signaling and tumor microenvironment in cervical Cancer

Cited by 26 publications

References 116 publications

Detection of CD39 and a Highly Glycosylated Isoform of Soluble CD73 in the Plasma of Patients with Cervical Cancer: Correlation with Disease Progression

Detection of CD39 and a Highly Glycosylated Isoform of Soluble CD73 in the Plasma of Patients with Cervical Cancer: Correlation with Disease Progression

The anticancer molecular mechanism of Carnosol in human cervical cancer cells: An in vitro study

Possible role of purinergic signaling in COVID-19

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