No abstract

Our data show that IFP is increased in tongue cancer. Corresponding changes in PTLV area, invasiveness, tumor area and IFP suggest that the increased pressure is caused by defective lymph drainage and solid stress generated by tumor cells growing in a low compliant environment.

Sympathetic nerves are known to affect carcinogenesis. Recently we found that sympathetic denervation decreases the size of rat tongue tumors. To identify genes involved in rat tongue carcinogenesis and to study the effect of sympathetic nerves on these genes, we compared gene-expression profiles in normal rat tongue (control) and in tumor-induced tongues with (SCGx) and without (Sham) bilateral sympathectomy. Significance analysis of microarrays revealed 280 genes (168 up-regulated, 112 down-regulated) that showed at least a twofold differential expression between Sham and SCGx tumors (false discovery rate < 5%). These included genes associated with cell adhesion, signaling, structure, proliferation, metabolism, angiogenesis, development, and immunity. Hierarchical clustering demonstrated that controls and sympathectomized tumors grouped together, while Sham tumors grouped separately. We identified 34 genes, known to be involved in carcinogenesis, that were not differentially expressed between sympathectomized tumors and control tongues, but which showed a significant change in expression in Sham tumors. Microarray results of 12 of these genes were confirmed by quantitative reverse transcription-polymerase chain reaction. In conclusion, sympathectomy significantly altered the gene-expression profile and inhibited tumor growth. The expression of several cancer genes were increased more than threefold in Sham tumors, but unaltered in the sympathectomized tumors when compared with controls, indicating that these genes may be of significance in rat tongue carcinogenesis.

No 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.