Activation of MMP-2 and MMP-9 in patients with oral squamous cell carcinoma.
OBJECTIVE
Oral cancer accounts for one third of all malignancies in India where habit of tobacco consumption is the major etiologic factor, which causes field cancerization in oral mucosa. Multiple molecular events in oral mucosa due to field cancerization may be the cause of local and regional lymph node involvement in oral cancer resulting into low overall survival, high recurrence rate, and poor prognosis. Several matrix metalloproteinases (MMPs) have been shown to play an important role in the invasion and metastasis of oral squamous cell carcinoma (SCC). MMP-2 and MMP-9 are capable of degrading type-IV collagen, which is a major component of basement membrane. Therefore, we studied MMP-2 and MMP-9 activation by gelatin zymography, which is cost effective alternate to ELISA method, in patients with oral SCCs to predict their role in metastatic potentials.


METHODS
Thirty-nine patients of oral SCCs were classified as non-metastatic (n = 28), and metastatic (n = 11) according to regional lymph node involvement. Malignant and adjacent normal tissues of the patients were collected at the time of surgery. Gelatin zymography was carried out using 7.5% polyacrylamide gel under non-denaturing and non-reducing conditions. Zymograms were analyzed densitometrically. Latent and active forms of MMP-2 and MMP-9 were expressed as ng/50 microg of protein.


RESULTS
Latent and active forms of MMP-2 and MMP-9 were significantly elevated in malignant tissues as compared to their adjacent normal tissues (P < 0.05). Total MMP-2 and MMP-9 activities were also significantly elevated in malignant tissues as compared to adjacent normal tissues (P = 0.005 and P = 0.028, respectively). Activation ratio of MMP-2 and MMP-9 were significantly elevated in malignant tissues as compared to adjacent normal tissues. Activation of MMP-2 was prominent (11%) than MMP-9 (5%) in malignant tissues. Activation ratio of MMP-2 was significantly elevated in patients with lymph node metastasis than patients without lymph node metastasis (P = 0.005). Receiver's operating characteristic (ROC) curve analysis revealed that activation ratio of MMP-2 discriminate better than and activation ratio of MMP-9 between patients with and without lymph node metastasis. Activation ratio of MMP-2 could predict risk of lymph node metastasis development in patients without lymph node involvement.


CONCLUSIONS
The study concluded that activation of MMP-2 and MMP-9 was significantly higher in malignant tissues as compared to adjacent normal tissues. Further, activation ratio of MMP-2 was significantly elevated in patients with lymph node metastasis as compared to patients without lymph node metastasis, which could predict risk of lymph node metastasis development in node negative patients.
Patel
Beena P
BP
Biochemistry Research Division, The Gujarat Cancer & Research Institute, Asarwa, Ahmedabad, India.
Shah
Pankaj M
PM
Rawal
Upendra M
UM
Desai
Amisha A
AA
Shah
Shakuntala V
SV
Rawal
Rakesh M
RM
Patel
Prabhudas S
PS
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000556:secondary; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9