Role of Cyclooxygenase-2 in Head and Neck Tumorigenesis

Frejborg, Ellen; Salo, Tuula; Salem, Abdelhakim

doi:10.3390/ijms21239246

Cited by 46 publications

(42 citation statements)

References 109 publications

(319 reference statements)

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“…They also observed higher mRNA level of TAM markers in HNSCC compared to the healthy pharyngeal tissue [57]. PTGS2 is a well-characterized enzyme whose upregulation in HNSCC has already been described [30,44,58]. Higher expression of the PTGS2 gene in HPV− tumors is in agreement with previously published data [44].…”

Section: Discussionsupporting

confidence: 87%

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ARG1 mRNA Level Is a Promising Prognostic Marker in Head and Neck Squamous Cell Carcinomas

et al. 2021

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Head and neck squamous cell carcinomas (HNSCC) can be induced by smoking or alcohol consumption, but a growing part of cases relate to a persistent high-risk papillomavirus (HPV) infection. Viral etiology has a beneficial impact on the prognosis, which may be explained by a specific immune response. Tumor associated macrophages (TAMs) represent the main immune population of the tumor microenvironment with a controversial influence on the prognosis. In this study, the level, phenotype, and spatial distribution of TAMs were evaluated, and the expression of TAM-associated markers was compared in HPV positive (HPV+) and HPV negative (HPV−) tumors. Seventy-three formalin and embedded in paraffin (FFPE) tumor specimens were examined using multispectral immunohistochemistry for the detection of TAM subpopulations in the tumor parenchyma and stroma. Moreover, the mRNA expression of TAM markers was evaluated using RT-qPCR. Results were compared with respect to tumor etiology, and the prognostic significance was evaluated. In HPV− tumors, we observed more pro-tumorigenic M2 in the stroma and a non-macrophage arginase 1 (ARG1)-expressing population in both compartments. Moreover, higher mRNA expression of M2 markers—cluster of differentiation 163 (CD163), ARG1, and prostaglandin-endoperoxide synthase 2 (PTGS2)—was detected in HPV− patients, and of M1 marker nitric oxide synthase 2 (NOS2) in HPV+ group. The expression of ARG1 mRNA was revealed as a negative prognostic factor for overall survival of HNSCC patients.

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Section: Discussionsupporting

confidence: 87%

“…Increased IDO1 expression correlates with poor prognosis in patients with colorectal [ 26 ], breast [ 25 ], endometrial [ 27 ], and ovarian carcinomas [ 28 ]. Higher PTGS2 expression has been associated with worse prognosis in many cancers including HNSCC [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

ARG1 mRNA Level Is a Promising Prognostic Marker in Head and Neck Squamous Cell Carcinomas

et al. 2021

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“…It is believed that COX2 can promote the development and progression of head and neck cancer. Therefore, COX2 inhibitors could be promising therapeutic weapons to fight the cancer [101].…”

Section: Prostaglandins In Other Cancermentioning

confidence: 99%

The Role of Prostaglandins in Different Types of Cancer

Jara-Gutiérrez

Baladrón

2021

Cells

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The prostaglandins constitute a family of lipids of 20 carbon atoms that derive from polyunsaturated fatty acids such as arachidonic acid. Traditionally, prostaglandins have been linked to inflammation, female reproductive cycle, vasodilation, or bronchodilator/bronchoconstriction. Recent studies have highlighted the involvement of these lipids in cancer. In this review, existing information on the prostaglandins associated with different types of cancer and the advances related to the potential use of them in neoplasm therapies have been analyzed. We can conclude that the effect of prostaglandins depends on multiple factors, such as the target tissue, their plasma concentration, and the prostaglandin subtype, among others. Prostaglandin D2 (PGD2) seems to hinder tumor progression, while prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2α) seem to provide greater tumor progression and aggressiveness. However, more studies are needed to determine the role of prostaglandin I2 (PGI2) and prostaglandin J2 (PGJ2) in cancer due to the conflicting data obtained. On the other hand, the use of different NSAIDs (non-steroidal anti-inflammatory drugs), especially those selective of COX-2 (cyclooxygenase 2), could have a crucial role in the fight against different neoplasms, either as prophylaxis or as an adjuvant treatment. In addition, multiple targets, related to the action of prostaglandins on the intracellular signaling pathways that are involved in cancer, have been discovered. Thus, in depth research about the prostaglandins involved in different cancer and the different targets modulated by them, as well as their role in the tumor microenvironment and the immune response, is necessary to obtain better therapeutic tools to fight cancer.

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“…COX-2 has also been considered as a promoter of vascular endothelial growth factors (VEGF) production, which would favor angiogenesis. Thus, selective COX-2 inhibitors represent promising therapeutics against cancer [ 21 ]. Moreover, high levels of reactive oxygen species (ROS) leading to aberrant redox signaling have been observed in many forms of cancer.…”

Section: Introductionmentioning

confidence: 99%

Toward Multitasking Pharmacological COX-Targeting Agents: Non-Steroidal Anti-Inflammatory Prodrugs with Antiproliferative Effects

et al. 2021

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The antitumor activity of certain anti-inflammatory drugs is often attributed to an indirect effect based on the inhibition of COX enzymes. In the case of anti-inflammatory prodrugs, this property could be attributed to the parent molecules with mechanism other than COX inhibition, particularly through formulations capable of slowing down their metabolic conversion. In this work, a pilot docking study aimed at comparing the interaction of two prodrugs, nabumetone (NB) and its tricyclic analog 7-methoxy-2,3-dihydro-1H-cyclopenta[b]naphthalen-1-one (MC), and their common active metabolite 6-methoxy-2-naphthylacetic acid (MNA) with the COX binding site, was carried out. Cytotoxicity, cytofluorimetry, and protein expression assays on prodrugs were also performed to assess their potential as antiproliferative agents that could help hypothesize an effective use as anticancer therapeutics. Encouraging results suggest that the studied compounds could act not only as precursors of the anti-inflammatory metabolite, but also as direct antiproliferative agents.

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Role of Cyclooxygenase-2 in Head and Neck Tumorigenesis

Cited by 46 publications

References 109 publications

ARG1 mRNA Level Is a Promising Prognostic Marker in Head and Neck Squamous Cell Carcinomas

ARG1 mRNA Level Is a Promising Prognostic Marker in Head and Neck Squamous Cell Carcinomas

The Role of Prostaglandins in Different Types of Cancer

Toward Multitasking Pharmacological COX-Targeting Agents: Non-Steroidal Anti-Inflammatory Prodrugs with Antiproliferative Effects

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