Characterization of 3 oral squamous cell carcinoma cell lines with different invasion and/or metastatic potentials.
OBJECTIVE
Proteolytic enzymes may confer specific types of invasion and metastasis in patients with oral squamous cell carcinoma (OSCC). The purpose of this study was to determine if OSCC that invades adjacent bone has different proteolytic enzyme expression profiles than OSCC that metastasizes to lymph nodes or distant organs. Three OSCC cell lines, BHY, HSC-3, and HN, with known behavior regarding bone invasion and lymph node and distant metastatic profiles, were evaluated. The characteristics of a control, human normal nasal epithelial cell line (HNEC), and BHY, HSC-3 and HN were evaluated with regard to their expression of the matrix metalloproteinases and cathepsins.


METHODS
Expressions of proteolytic enzymes including matrix metalloproteinase, MMP-1, MMP-2, MMP-3, MMP-9, extracellular matrix metalloproteinase inducer (EMMPRIN), cathepsin B, and cathepsin L were compared using immunocytochemistry and flow cytometry in 3 OSCC cell lines and HNEC. The cell morphologies of these 4 cell lines were compared using transmission electron microscopy (TEM).


RESULTS
All OSCC cell lines showed higher expression of all the proteolytic proteins when compared with HNEC, except the HSC-3 cell line showed no difference in the expression of MMP-9. There was no detectable difference at the expression level of MMP-1, MMP-2, MMP-3, cathepsin B, and cathepsin L in any of the OSCC cell lines. However, MMP-9 and EMMPRIN levels were higher in the BHY cell line. According to electron microscopy, the cells of the HSC-3 cell line were the smallest and least differentiated among the 3 OSCC cell lines. The BHY cell line was the most highly differentiated showing interdigitation and numerous cell junctions.


CONCLUSIONS
MMPs play an important role in the invasion and metastasis of oral cancer. MMP-9 might play a more important role than MMP-2 during invasion. Increased expression of MMP-1, MMP-9, and EMMPRIN proteins might be involved in invasion of OSCC to adjacent bone, as they are necessary for the collagen matrix degradation. Increased expression of MMP-3, cathepsin B and L in OSCC might be associated with both invasion and a high incidence of metastasis.
Erdem
N Fazil
NF
Department of Oral and Maxillofacial Surgery, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USA.
Carlson
Eric R
ER
Gerard
David A
DA
Ichiki
Albert T
AT
D000328:Adult; D051926:Basigin / Q000096:biosynthesis; D001859:Bone Neoplasms / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000556:secondary* / Q000648:ultrastructure; D002403:Cathepsins / Q000096:biosynthesis*; D045744:Cell Line, Tumor / Q000201:enzymology / Q000648:ultrastructure; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000096:biosynthesis*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000648:ultrastructure; D009361:Neoplasm Invasiveness
D051926:Basigin; D002403:Cathepsins; D053505:Matrix Metalloproteinases, Secreted