Oncogenic effects of PAFR ligands produced in tumours upon chemotherapy and radiotherapy

Chammas, Roger; Andrade, Luciana Nogueira de Sousa; Jancar, Sônia

doi:10.1038/nrc.2017.15

Cited by 17 publications

(8 citation statements)

References 13 publications

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“…Based on these studies, we propose that the PAF/PAFR axis may constitute an important route for acquired resistance after chemo- and radiotherapy in a direct or indirect manner, as highlighted previously 74 . The combined use of PAFR antagonists with radio- or chemotherapeutic agents may be a promising strategy against cancer, increasing the radio- and chemotherapeutic effectiveness.…”

Section: Pafr and Tumor Repopulation After Chemo- And Radiotherapysupporting

confidence: 63%

Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy

Silva¹,

Andrade²,

Jancar³

et al. 2018

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Platelet activating factor is a lipid mediator of inflammation, and in recent decades, it has emerged as an important factor in tumor outcomes. Platelet activating factor acts by specific binding to its receptor, which is present in both tumor cells and cells that infiltrate tumors. Pro-tumorigenic effects of platelet activating factor receptor in tumors includes promotion of tumor cell proliferation, production of survival signals, migration of vascular cells and formation of new vessels and stimulation of dendritic cells and macrophages suppressor phenotype. In experimental models, blocking of platelet activating factor receptor reduced tumor growth and increased animal survival. During chemotherapy and radiotherapy, tumor cells that survive treatment undergo accelerated proliferation, a phenomenon known as tumor cell repopulation. Work from our group and others showed that these treatments induce overproduction of platelet activating factor-like molecules and increase expression of its receptor in tumor cells. In this scenario, antagonists of platelet activating factor markedly reduced tumor repopulation. Here, we note that combining chemo- and radiotherapy with platelet activating factor antagonists could be a promising strategy for cancer treatment.

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Section: Pafr and Tumor Repopulation After Chemo- And Radiotherapysupporting

confidence: 63%

Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy

Silva¹,

Andrade²,

Jancar³

et al. 2018

Clinics

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“…Furthermore, activation of PAFR in macrophages promotes reprogramming towards an anti‐inflammatory and pro‐tumorigenic profile (M2 phenotype). Irradiation and chemotherapy generate a wide range of PAFR ligands (PAF‐like) in the tumour microenvironment that act as PAFR agonists, amplifying the effect of PAFR activation in tumour cells and macrophages (Chammas, de Sousa Andrade, & Jancar, ).…”

Section: Tumour Repopulationmentioning

confidence: 99%

Oncometabolites in cancer aggressiveness and tumour repopulation

et al. 2019

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Tumour repopulation is recognized as a crucial event in tumour relapse where therapy-sensitive dying cancer cells influence the tumour microenvironment to sustain therapy-resistant cancer cell growth. Recent studies highlight the role of the oncometabolites succinate, fumarate, and 2-hydroxyglutarate in the aggressiveness of cancer cells and in the worsening of the patient's clinical outcome. These oncometabolites can be produced and secreted by cancer and/or surrounding cells, modifying the tumour microenvironment and sustaining an invasive neoplastic phenotype. In this review, we report recent findings concerning the role in cancer development of succinate, fumarate, and 2-hydroxyglutarate and the regulation of their related enzymes succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase. We propose that oncometabolites are crucially involved in tumour repopulation. The study of the mechanisms underlying the relationship between oncometabolites and tumour repopulation is fundamental for identifying efficient anti-cancer therapeutic strategies and novel serum biomarkers in order to overcome cancer relapse.

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“…Finally, PAF activates the PAF receptor (PAFR), which belongs to the superfamily of GPCRs ( 14 , 15 ). Inappropriate activation of the PAF-PAFR axis is thought to play an important role in cancer biology, tumor radioresistance, and modulation of the tumor microenvironment ( 16 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

Interplay Between EGFR and the Platelet-Activating Factor/PAF Receptor Signaling Axis Mediates Aggressive Behavior of Cervical Cancer

et al. 2020

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Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in cervical tumors, being correlated with adverse clinical outcomes. EGFR may be activated by a diversity of mechanisms, including transactivation by G-protein coupled receptors (GPCRs). Studies have also shown that platelet-activating factor (PAF), a pro-inflammatory phospholipid mediator, plays an important role in the cancer progression either by modulating the cancer cells or the tumor microenvironment. Most of the PAF effects seem to be mediated by the interaction with its receptor (PAFR), a member of the GPCRs family. PAFR- and EGFR-evoked signaling pathways contribute to tumor biology; however, the interplay between them remains uninvestigated in cervical cancer. In this study, we employed The Cancer Genome Atlas (TCGA) and cancer cell lines to evaluate possible cooperation between EGFR, PAFR, and lysophosphatidylcholine acyltransferases (LPCATs), enzymes involved in the PAF biosynthesis, in the context of cervical cancer. It was observed a strong positive correlation between the expression of EGFR × PAFR and EGFR × LPCAT2 in 306 cervical cancer samples. The increased expression of LPCAT2 was significantly correlated with poor overall survival. Activation of EGFR upregulated the expression of PAFR and LPCAT2 in a MAPK-dependent fashion. At the same time, PAF showed the ability to transactivate EGFR leading to ERK/MAPK activation, cyclooxygenase-2 (COX-2) induction, and cell migration. The positive crosstalk between the PAF-PAFR axis and EGFR demonstrates a relevant linkage between inflammatory and growth factor signaling in cervical cancer cells. Finally, combined PAFR and EGFR targeting treatment impaired clonogenic capacity and viability of aggressive cervical cancer cells more strongly than each treatment separately. Collectively, we proposed that EGFR, LPCAT2, and PAFR emerge as novel targets for cervical cancer therapy.

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Oncogenic effects of PAFR ligands produced in tumours upon chemotherapy and radiotherapy

Cited by 17 publications

References 13 publications

Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy

Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy

Oncometabolites in cancer aggressiveness and tumour repopulation

Interplay Between EGFR and the Platelet-Activating Factor/PAF Receptor Signaling Axis Mediates Aggressive Behavior of Cervical Cancer

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