title: Pathophysiology of oral cancer in experimental animal models: a review with focus on the role of sympathetic nerves.
abstract: Global increase in incidence and mortality as well as poor prognosis of oral cancer (OC) has intensified efforts towards early detection and prevention of this disfiguring disease. Several studies have been conducted using experimental animal models to understand the pathophysiology and molecular events involved in OC. Lack of identification of specific biomarkers during the multifaceted steps of oral carcinogenesis has hindered its diagnosis and treatment. Solid stress generated by growing tumors as well as abnormalities in tumor vasculature lead to increased interstitial fluid pressure, which could obstruct therapeutic drug delivery to tumors. Furthermore, the sympathetic nervous system is known to affect angiogenesis, vessel permeability, immune responses and carcinogenesis. Recent findings indicate that, in addition to angiogenic and lymphangiogenic factors, tumor cells release neurotrophic factors that initiate innervation. Interactions between cytokines and sympathetic neurotransmitters, and their respective receptors expressed by the nerve, immune and tumor cells appear to influence tumor growth. Thus, understanding the complex signaling processes and interrelationships between vascular, nervous and immune systems during oral carcinogenesis may prove vital for successful prevention and treatment of OC. This review aims at outlining the available knowledge on pathophysiology of OC in experimental animal models including evidence from our own findings.
authors.affiliation: Department of Biomedicine, Section for Biochemistry and Molecular Biology, University of Bergen, Bergen, Norway.
authors.forename: Bina
authors.initials: B
authors.lastname: Raju
authors.forename: Salah O
authors.initials: SO
authors.lastname: Ibrahim
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000502:physiology*; D018925:Chemokines / Q000502:physiology; D004195:Disease Models, Animal; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D009055:Mouth / Q000294:innervation*; D009062:Mouth Neoplasms / Q000503:physiopathology*; D009374:Neoplasms, Experimental / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000502:physiology* / Q000503:physiopathology
chemical_list: D014408:Biomarkers, Tumor; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins