Increased expression of matrix metalloproteinase-2 in oral cells after short-term stimulation and long-term usage of areca quid.
OBJECTIVE
Arecoline, an areca quid (AQ) component, has been shown to inhibit the secretion and activity of matrix metalloproteinase-2 (MMP-2) in fibroblast cultures. This study assessed whether MMP-2 expression was inhibited in the saliva samples and tumor specimens of oral tumor patients with a long-term history of AQ consumption. The net effect of crude AQ extract (AQE) on MMP-2 expression by oral cells was also investigated.


METHODS
Western blot analysis, zymography, and reverse transcriptase-polymerase chain reaction were used to detect MMP-2 protein and mRNA in saliva and tumor samples, as well as in the conditioned media (CM) of oral cell cultures.


RESULTS
The level of MMP-2 protein was significantly higher in the saliva samples of 12 oral tumor patients who had a minimum 10-year AQ-consuming history than in those of 12 non-AQ-using healthy controls (p < 0.05). MMP-2 mRNA was expressed in 26 of 28 oral squamous cell carcinoma (OSCC) specimens. MMP-2 protein was also detectable in the tested OSCC homogenates. Short-term stimulation with 10% AQE increased the secretion of MMP-2 protein in the CM of oral epidermoid carcinoma cell Meng-1 (an OSCC cell line) and oral fibroblasts.


CONCLUSIONS
MMP-2 expression is elevated rather than inhibited in most oral tumor patients with long-term AQ usage. Short-term AQE stimulation also increases the secretion of MMP-2 by oral epithelial cells and fibroblasts. Our results suggest that AQ consumption may promote oral tumor progression through the induction of MMP-2 secretion.
Liu
Shyun-Yeu
SY
Oral and Maxillofacial Section, Chi-Mei Medical Center, Tainan, Taiwan.
Lin
Mei-Huei
MH
Yang
Shun-Chun
SC
Huang
Guan-Cheng
GC
Chang
Lisa
L
Chang
Sam
S
Yen
Ching-Yu
CY
Chiang
Wei-Fan
WF
Kuo
Yung-Yen
YY
Chen
Li-Lin
LL
Lee
Chin-Hai
CH
Liu
Young-Chau
YC
D001114:Areca; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000209:etiology; D015870:Gene Expression; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000209:etiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012463:Saliva / Q000201:enzymology*
D020778:Matrix Metalloproteinase 2