Matrix metalloproteinase 2 and matrix metalloproteinase 9 expression in human oral squamous cell carcinoma and the effect of protein kinase C inhibitors: preliminary observations.
OBJECTIVE
The purpose of this study was to investigate gelatinase (matrixmetalloproteinase [MMP]-2 and MMP-9) expression in oral squamous cell carcinoma (OSCC) and to explore the mechanisms that may inhibit gelatinase activity.


METHODS
Thirty biopsy specimens of OSCCs were examined by means of immunohistochemistry. Supernatants from primary cultures of human oral mucosal keratinocyte and oral cancer-derived cells (KB and OC2) were analyzed by means of gelatin zymography. Furthermore, protein kinase C (PKC) inhibitors (H7 and staurosporine) were added to test how they modulate gelatinase production in human oral cancer cells.


RESULTS
MMP-2 and MMP-9 expression was significantly higher in oral SCCs and was located in discrete clusters of tumor cells. Oral mucosal keratinocyte cultures, KB, and OC2 were found to secrete and produce MMP-2 and MMP-9. However, the amounts of MMP-2 and MMP-9 were highly elevated in the 2 oral cancer cell lines in comparison with oral mucosal keratinocyte cultures (P <.05). In addition, PKC inhibitors were found to decrease MMP-2 and MMP-9 activities in oral cancer cells (P <.05).


CONCLUSIONS
Taken together, human oral SCCs produce MMP-2 and MMP-9 in vivo and in vitro, and gelatinase activity is down-regulated by PKC inhibitors in vitro. PKC inhibitors suppressing MMP production and/or activity may represent valuable therapeutic agents through their influence on the pathogenesis of OSCC. These agents may prove clinically useful in combination with standard therapeutic modalities for the treatment of patients with oral cancer.
Tsai
Chung-Hung
CH
Chung Shan Medical University, Taichung, Taiwan. cyc@csmu.edu.tw
Hsieh
Yih-Shou
YS
Yang
Shun-Fa
SF
Chou
Ming-Yung
MY
Chang
Yu-Chao
YC
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D018929:Cell Culture Techniques; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D061965:Matrix Metalloproteinase Inhibitors; D009061:Mouth Mucosa / Q000166:cytology / Q000201:enzymology; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019311:Staurosporine