The Biological Significance Of Neurogenesis In Human Oral Squamous Cell Carcinoma

OBJECTIVE To reveal the neurogenesis and its clinicopathological significance in human oral squamous cell carcinoma(OSCC)by detecting the expression of protein gene product(PGP)9.5 and S100.To explore the potential relationship between neurogenesis and immunological function in tumor microenvironment by assessing the correlation between the number of dendritic cells with the expression of PGP9.5 in OSCC.To investigate the direct effects of calcitonin gene related peptide(CGRP)on the migration and invasion ability of TSCCA cells and its underlying molecular mechanisms.METHODS The immunohistochemistry for PGP9.5 and S100 used to identify nerve fibers and dendritic cells was performed on whole tissue sections in 167 cases of OSCC.The correlation between the expression of PGP9.5 and the clinicopathological features of OSCC was evaluated,and the relationship between the expression of PGP9.5 and the number of dendritic cells was also explored.The effects of CGRP on the migration and invasion of TSCCA cells were detected by cell scratch assay and Transwell assays.The effects of CGRP on the expression of phosphorylated mitogen-activated protein kinases(MAPKs)signaling including p-ERK,p-p38 and p-JNK in TSCCA cells were examined using Western Blot.RESULTS Immunohistochemistry showed that PGP9.5 was expressed in 88%(147/167)of OSCC,mainly distributed in the tumor stroma.The expression of PGP9.5 was much higher in grades 2-3 tumors than in grade 1 tumors(P <0.000).In addition,the moderate / strong expression of PGP9.5 and tumor invasion(P = 0.034)or shorter patients' survival(P = 0.038)were closely related.Moreover,the moderate / strong expression of PGP9.5 was found to be significantly related to the increased number of dendritic cells in intratumoral region(P = 0.0014),peritumoral region(P = 0.0002)and intra-epithelial region(P = 0.019).CGRP was shown to promote the migration(P <0.05)and invasion(P <0.001)of TSCCA cells by cell scratch assay and Transwell assay,respectively.Western Blot results revealed that the expression of p-ERK(P <0.001),p-p38(P <0.05)and p-JNK(P <0.05)was increased in TSCCA cells at 1h,6h and 24 h after CGRP treatment,respectively.CINCLUSIONS Neurogenesis does occur in human oral squamous cell carcinoma and is related to tumor grade,neural invasion and patient survival.The correlation between dendritic cells and neurogenesis suggests the influence of nervous system on immunologic functions in tumor microenvironment.CGRP promotes the migration and invasion of oral squamous cell carcinoma cells through phosphorylation of MAPK signaling pathways.