Nerve growth factor and tyrosine kinase A in human salivary adenoid cystic carcinoma: expression patterns and effects on in vitro invasive behavior.
OBJECTIVE
Perineural invasion is a frequent occurrence in salivary adenoid cystic carcinoma (ACC) and may prevent complete surgical resection. Studies have indicated that nerve growth factor (NGF) and its high-affinity receptor tyrosine kinase A (TrkA) may play a role in perineural invasion in several malignancies in which perineural invasion is observed. The present study was conducted to investigate the expression of NGF and TrkA in salivary ACC and to examine the effects of NGF on adhesion, migration and invasion capacities of a salivary ACC cell line (SACC-83) in vitro.


METHODS
Expression of NGF and TrkA was explored using immunohistochemistry in paraffin-embedded tissues of 32 cases of salivary ACC. The effects of NGF on in vitro adhesion, migration, and invasion capacities of the SACC-83 cell line were examined using an MTT assay and a modified Boyden chamber assay respectively.


RESULTS
In ACC specimens, 31 (96.9%) and 32 (100%) tumors showed immunoreactivity for NGF and TrkA respectively. Significant correlations were found between NGF/TrkA expression levels and perineural invasion (P < .05). In cell adhesion assay, the percent adherences of SACC-83 cells co-cultured with 25 ng/ml NGF at 1.5 hours and 5, 25 ng/ml NGF at 6 hours were significantly higher than that co-cultured with 0 ng/ml NGF (P < .05). However, high concentration of NGF (500 ng/ml) resulted in a significant inhibition of invasion (P < .05).


CONCLUSIONS
Overexpression of NGF and TrkA in human salivary ACC tissues may constitute a reason for perineural invasion in salivary ACC.
Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, P.R. China.
Lei
L
Wang
Moyi
M
Sun
Yuegui
Y
Jiang
Lianjia
L
Yang
Delin
D
Lei
Chao
C
Lu
Yinghua
Y
Zhao
Pu
P
Zhang
Yaowu
Y
Yang
Jianhu
J
Li
D016475:3T3 Cells; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor; D003528:Carcinoma, Adenoid Cystic / Q000378:metabolism / Q000556:secondary*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000494:pharmacology; D010524:Peripheral Nervous System Neoplasms / Q000556:secondary*; D020917:Receptor, trkA / Q000096:biosynthesis*; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D020932:Nerve Growth Factor; D020917:Receptor, trkA