Intersecting Mechanisms of Hypoxia and Prostaglandin E2-Mediated Inflammation in the Comparative Biology of Oral Squamous Cell Carcinoma

Abstract

The importance of inflammation in the pathogenesis of cancer was first proposed by Rudolph Virchow over 150 years ago, and our understanding of its significance has grown over decades of biomedical research. The arachidonic acid pathway of inflammation, including cyclooxygenase (COX) enzymes, PGE2 synthase enzymes, prostaglandin E2 (PGE2) and PGE2 receptors has been extensively studied and has been associated with different diseases and different types of cancers, including oral squamous cell carcinoma (OSCC). In addition to inflammation in the tumour microenvironment, low oxygen levels (hypoxia) within tumours have also been shown to contribute to tumour progression. Understandably, most of our OSCC knowledge comes from study of this aggressive cancer in human patients and in experimental rodent models. However, domestic animals develop OSCC spontaneously and this is an important, and difficult to treat, form of cancer in veterinary medicine. The primary goal of this review article is to explore the available evidence regarding interaction between hypoxia and the arachidonic acid pathway of inflammation during malignant behaviour of OSCC. Overlapping mechanisms in hypoxia and inflammation can contribute to tumour growth, angiogenesis, and, importantly, resistance to therapy. The benefits and controversies of anti-inflammatory and anti-angiogenic therapies for human and animal OSCC patients will be discussed, including conventional pharmaceutical agents as well as natural products.

Genomic landscape and gene expression profiles of feline oral squamous cell carcinoma

“…Transcriptional profiling showed that FOSCC is enriched with genes known to be upregulated in Human OSCC ( 34 ) suggesting conserved gene regulatory mechanisms. While these findings were predicted given the remarkable clinical, pathological, and genetic parallels between both tumors ( 9 , 37 , 60 – 62 ) they in no way confirm comparative origins or outcomes. The functional gene and canonical pathway enrichment analyses provided us further insight into the possible activation of several pathways that were seen in FOSCC that included EMT, hypoxia- and inflammation-related pathways ( 61 – 65 ), indicating the complementary value of gene expression analysis in this study.…”

Pretreatment Glasgow Prognostic Score Correlated with Serum Histidine Level and Three-Year Mortality of Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma and Optimal Performance Status

“…Released from HNC and immune cells, vascular endothelial growth factor (VEGF) directly inhibits T cell development, including thymocyte maturation and differentiation [ 79 ], while IL-6 promotes platelet formation [ 80 ]. Further, PGE2 released from HNC cells can autocrinally induce the production of hypoxia-inducible factors and VEGF, which, subsequently, generates reactive oxygen species (ROS) from regulatory T cells, macrophages, and myeloid-derived suppressor cells within tumor tissue and in the peripheral blood [ 81 , 82 ]. The balance between the consumption and production of ROS determines T cell proliferation and function [ 81 ] and the initiation of thrombopoiesis from mature megakaryocytes in the bone marrow [ 83 ].…”

Feline Oral Squamous Cell Carcinoma: A Critical Review of Etiologic Factors

“…During the inflammatory process, mediators such as cytokines, prostaglandins, and matrix metalloproteinases (MMP) are released and pro-inflammatory transcription factors are activated, such as NF-κB and the transducer and transcription activator signal 3 (STAT3), which play an important role in suppressing apoptosis, proliferation, angiogenesis, invasion, and tumor metastasis. Some studies, in vivo and in vitro, have demonstrated the deregulation of COXs [ 6 ], STAT3 [ 62 ], EGFR [ 63 ], VEGF [ 64 ], and CD147 [ 65 ] in FOSCC samples.…”