Expression of MMPS, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: correlations with tumor invasion and metastasis.
BACKGROUND
Matrix metalloproteinases (MMPs) that degrade the extracellular matrices (ECMs) have been thought to play an important role in both the invasion and metastasis of tumors. However, the detailed role of MMPs and TIMPs (tissue inhibitors of MMP) on the biological behavior of tumor cells has yet to be elucidated in vivo. The aim of the present study was thus to determine whether expression of MMPs on tumor cells is associated with such clinicopathological features as the invasive and metastatic potential.


METHODS
This study included 96 cases of primary oral squamous cell carcinoma (OSCC), of which 38 cases showed lymph node metastases. The relationship between the expression of MMPs and the staining of ECMs, the mode of tumor invasion, nodal involvement, and expression of TIMPs was immunohistochemically examined.


RESULTS
First of all, a decrease in the staining of ECMs was observed in cases with an increased expression of MMP-1, -2, and -9. The association between the expression of MMPs and the loss of ECMs was thus found to be statistically significant. Secondly, in both invasive and metastatic cases, a marked expression of MMP-1, -2, -3, -9 and MT1-MMP was frequently observed. The association of the expression of MMPs both with the mode of tumor invasion and nodal involvement was thus found to be statistically significant. Thirdly, TIMP-2 was thus found not to significantly decrease in metastatic cases, while TIMP-1 expression significantly increased in metastatic cases.


CONCLUSIONS
These results suggest that tumor progression is dependent on the ability of tumor cells to degrade ECMs, while the metastasis of tumors is regulated by many types of MMPs, and the overproduction of MMPs therefore appears to be more important for metastasis than the production of TIMPs in vivo.
Kurahara
S
S
Second Department of Oral and Maxillofacial Surgery Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
Shinohara
M
M
Ikebe
T
T
Nakamura
S
S
Beppu
M
M
Hiraki
A
A
Takeuchi
H
H
Shirasuna
K
K
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000473:pathology* / Q000556:secondary; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000032:analysis*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012680:Sensitivity and Specificity; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis*
D014408:Biomarkers, Tumor; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2