Nerve Growth Factor and Tyrosine Kinase A in Human Salivary Adenoid Cystic Carcinoma: Expression Patterns and Effects on In Vitro Invasive Behavior
Purpose
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.
Patients and 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).
Conclusion
Overexpression of NGF and TrkA in human salivary ACC tissues may constitute a reason for perineural invasion in salivary ACC.
⁎Doctoral Student, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi’an, P.R. China
†Professor, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi’an, P.R. China
‡Associate Professor, Department of Conservative Dentistry, School of Stomatology, Xi’an Jiaotong University, Xi’an, P.R. China
§Professor, Department of Oral Pathology, School of Stomatology, Fourth Military Medical University, Xi’an, P.R. China
∥Professor and Chairman, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi’an, P.R. China
¶Research Associate, Department of Oral Anatomy and Physiology, School of Stomatology, Fourth Military Medical University, Xi’an, P.R. China
#Doctoral Student, Department of Prosthetic Dentistry, School of Stomatology, Fourth Military Medical Univeristy, Xi’an, P.R. China
⁎⁎Associate Professor, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi’an, P.R. China
††Associate Professor, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi’an, P.R. China
‡‡Attending Doctor, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi’an, P.R. China
Address correspondence and reprint requests to Dr Sun: Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Kang Fu Road 7, Xi’an 710032, P.R. China
This study was supported by grants from the National Natural Science Foundation of China (No. 30271424) and the Natural Science Foundation of Shannxi Province of China (No. 2002C2-06).
ABSTRACT