May High MMP-2 and TIMP-2 Expressions Increase or Decrease the Aggressivity of Oral Cancer?

Matrix metalloproteinases-2 (MMP-2) and the tissue inhibitor of metalloproteinase-2 (TIMP-2), may presumably have an important role on the invasion and metastatic spread of malignancies attributed to an uncontrolled degradation of the extracellular matrix (ECM). A retrospective chart analysis was carried out to study the expression of MMP-2 and TIMP-2 on the archival samples of oral squamous cell carcinoma (OSCC) (n = 30) and normal mucosa (n = 10) by immunohistochemistry and compared with the clinicopathologic parameters of cases. Both MMP-2 and TIMP-2 expressions showed a positive correlation with the grades, stages and metastatic capacities of tumors (Spearman's correlation, p < 0.05). Concomitant increase in the expression of TIMP-2 and MMP-2 suggested that the rate of MMP-2/TIMP-2 expression is a better marker for characterization of MMP-2 concentration. High expression and/or activity of MMP-2 were linked with poorer survival in OSCC cases, while TIMPs have been shown to apparently act as either growth-stimulating or suppressor factors for tumors. It was also revealed that MMP-2 and TIMP-2 were secreted by both tumor cells and stromal cells. A new concept, supposing the dynamic, anticancer partnership between the residual genome stabilizer machinery of tumor cells and defensive cells adjacent to tumors, may illuminate the controversial results. In conclusion, the stronger the infiltrative and metastatic capacity of cancers, the higher is the rate of MMP-2/TIMP-2 expression helping the arrival of humoral and cellular anticancer forces.