Vascular Endothelial Growth Factor: A Translational View in Oral Non-Communicable Diseases

Abstract

Vascular endothelial growth factors (VEGFs) are vital regulators of angiogenesis that are expressed in response to soluble mediators, such as cytokines and growth factors. Their physiologic functions include blood vessel formation, regulation of vascular permeability, stem cell and monocyte/macrophage recruitment and maintenance of bone homeostasis and repair. In addition, angiogenesis plays a pivotal role in chronic pathologic conditions, such as tumorigenesis, inflammatory immune diseases and bone loss. According to their prevalence, morbidity and mortality, inflammatory diseases affecting periodontal tissues and oral cancer are relevant non-communicable diseases. Whereas oral squamous cell carcinoma (OSCC) is considered one of the most common cancers worldwide, destructive inflammatory periodontal diseases, on the other hand, are amongst the most prevalent chronic inflammatory conditions affecting humans and also represent the main cause of tooth loss in adults. In the recent years, while knowledge regarding the role of VEGF signaling in common oral diseases is expanding, new potential translational applications emerge. In the present narrative review we aim to explore the role of VEGF signaling in oral cancer and destructive periodontal inflammatory diseases, with emphasis in its translational applications as potential biomarkers and therapeutic targets.

IL-1/IL-1R Signaling in Head and Neck Cancer

“…The main functions of IL-1β are to induce upregulation of cytokines, chemokines, adhesion molecules, acute phase proteins and tissue remodeling enzymes [ 17 , 49 , 52 ]; it may also act as an angiogenic factor in tumors [ 53 ], inducing the production of vascular endothelial growth factor (VEGF) via cyclooxygenase (COX)-2 activation [ 54 ]. IL-1β has been associated with the pathobiology of many diseases, such as familial periodic fever syndromes [ 55 ], multiple organ failure in sepsis [ 56 ], rheumatoid arthritis, type II diabetes [ 57 ], chronic obstructive pulmonary disease [ 58 ] and growth, vascularization and metastasis of malignant tumors [ 53 ].…”

Amygdalin potentiates the anti-cancer effect of Sorafenib on Ehrlich ascites carcinoma and ameliorates the associated liver damage

“…Sorafenib (Sor) is a drug that has been shown to prolong overall survival in patients with advanced liver cancer. Sorafenib is an oral multi-kinase inhibitor exerting its effects via RAF/MEK/ERK pathway 15 , vascular endothelial growth factor receptor (VEGFR) 16 , and platelet-derived growth factor receptor beta (PDGFR-β) tyrosine kinases 17 . Little data are available in the literature regarding the combined effect of Amy and Sor against tumor burden and the liver damage induced by EAC.…”

Vascular permeability in HPV+ oropharyngeal cancers aids in fluorescent image‐guided transoral robotic surgery using indocyanine green

“…However, as mentioned earlier, the gap in knowledge lies in the identification of the underlying vascular characteristics that drive the ICG accumulation in the head and neck tumors. Hence, one of the objectives of this study was to explore the underlying molecular mechanism and evaluate the expression of pro‐angiogenic markers that contribute towards the vascular dysregulation in HPV+ OPSCCa specifically, as the relationship between pro‐angiogenic genes specially VEGF and oral cancers is well‐established 46–49 . The role of HPV in cancer progression has been widely studied, demonstrating the virus's ability to affect the epithelial cell replication cycle, as well as activate E6 oncoprotein in a p53‐independent manner 50 .…”

“…Hence, one of the objectives of this study was to explore the underlying molecular mechanism and evaluate the expression of pro-angiogenic markers that contribute towards the vascular dysregulation in HPV+ OPSCCa specifically, as the relationship between pro-angiogenic genes specially VEGF and oral cancers is well-established. [46][47][48][49] The role of HPV in cancer progression has been widely studied, demonstrating the virus's ability to affect the epithelial cell replication cycle, as well as activate E6 oncoprotein in a p53-independent manner. 50 E6 in turn activates VEGF, which is known to stimulate angiogenesis.…”