Research On The Function Of Matrix Metalloproteinases-12 In Melanoma

Cutaneous melanoma constitutes the highest malignant type of skin cancer due to its strong aggressiveness. According to the world health organization(WHO), the speed of increase in the number of melanoma patients is higher than any other types of cancer around the world, in recent years. And according to statistical estimation, the incidence of melanoma will probably be doubled in the next 10 to 20 years. Although melanoma accounts for only about 5% of all cases of skin cancer, the total death caused by melanoma accounted for as many as 74% of cases of skin cancer deaths. In patients with melanoma of early diagnosis, the patient’s clinical prognosis is usually good, such as in stage I melanoma 5-year survival rate can reach 90%. But with the progress of this tumor, the 5-year survival rate of melanoma quickly reduces, such as in stage II melanoma, the 5-year survival rate is about 60%, and the 5-year survival rate for stage III melanoma is merely 10%. While in the highest malignant degree of stage IV melanoma, there was almost no one survived to five years. This characteristic indicates that the invasion and metastasis of melanoma malignant biological behavior is the important reason of poor prognosis. Therefore, in-depth study of the molecular mechanism for regulation of invasion and metastasis of melanoma, which plays a key role in these malignantbiological behavior, would not only provide available prognostic biomarkers for tailored melanoma treatment, can also shed light on future targeted intervention for the invasion and metastasis.Matrix metalloproteinases are a proteolytic enzyme gene families, this kind of proteolytic enzyme activity depends on the zinc ions, is the most common degradation of extracellular matrix of protease, matrix metalloproteinases role is the main biological specificity of various components in the degradation of extracellular matrix. The vast majority of cells in the normal physiological condition not reserve matrix metalloproteinases, temporary synthesis of matrix metalloproteinases is when the body appear all sorts of need in the cell. Matrix metalloproteinases in the body in the first place in the form of inactive enzymes original secreted to the outside of the cell, and then split by protease hydrolysis into activation in the form of matrix metalloproteinases. In an organism’s physiological and pathological process, such as embryonic development, cartilage ossification, angiogenesis and wound healing and tissue remodeling, the expression of matrix metalloproteinases can play an important role. In addition, in all kinds of tumor, matrix metalloproteinases present high expression or and highly active. The tumor is a complex multi-step process, in the process of tumor cells to the malignant cell differentiation, tumor cells gradually through the basement membrane and extracellular matrix. Basement membrane and extracellular matrix protein degradation is an important step, from the need of protease involved. Invasive tumor growth and metastasis of the basic process is: first of all, on the basis of the primary tumor to deep invasive growth, after the invasion of tumor cell invasion through matrix and enter lymphatic or blood vessel system, along with the lymph circulation or circulation of the blood to the tissues and organs to grow and formation of metastases. In this process, extracellular matrix forming a barrier structure block tumor cell invasion, the action of qualified tumor in the primary site. Due to the matrix metalloproteinases are the main biological activities of specific degradation of extracellular matrix, and have the function of the regulation of tumor angiogenesis form, therefore in the process of invasion andmetastasis of tumor, members of the family of matrix metalloproteinases is the most important protease degradation of extracellular matrix. Members of the family of matrix metalloproteinases with peptide enzyme activity, can be widely the degradation of extracellular matrix, and the main components of the basement membrane, not only in the normal tissue and cell has a role in physiological and pathological process, but also play an important role in tumor invasion and metastasis, therefore has been widely research. At present, it has been found that there were 28 members in family of matrix metalloproteinases. Among these matrix metalloproteinases members, the substrate and effect of each member is not the same. Thus, clearly understand the role of matrix metalloproteinases family members can offer a theoretical basis to know the molecular mechanism of tumor invasion and metastasis. Matrix metalloproteinases-12, as a member of the family of matrix metalloproteinases, the expression pattern and clinical significance in the melanoma has not been addressed yet. In the present study, to illustrate the pattern and potential role of matrix metalloproteinases-12 in melanoma, we examined the protein expression level of matrix metalloproteinases-12 in clinical specimens of melanoma, analyzed the association between matrix metalloproteinases-12 expression and clinical features. The cellular function of matrix metalloproteinases-12 and its potential regulation by CD147 was verified in A-375 melanoma cell lines in order to clarify its role on tumor cell invasion ability and regulation mechanism.Experimental results showed that the expression of matrix metalloproteinases-12 in melanoma is significantly higher than that in normal skin tissues. And the expression level of matrix metalloproteinases-12 in melanoma was significantly associated with the depth of tumor invasion, lymph node metastasis, distant metastasis and clinical stage, as high expression of matrix metalloproteinases-12 was more likely to be detected in melanoma of deep invasion, lymph node and distant metastasis, advanced clinical stage. In order to validate cellular effect matrix metalloproteinases-12 in melanoma cell lines. We manually interferenced the expression of matrix metalloproteinases-12 in human melanoma A-375 cell lines by stealth RNAi. Then, transwell assay revealed that decrease of matrix metalloproteinases-12 expression can significantly inhibit the invasive abilityof human melanoma cells. In addition, the expression level of matrix metalloproteinases-12 was significantly decreased after the down regulation of CD147 in A-375 cell lines.The above results proved that matrix metalloproteinases-12 expression in human melanoma was significantly increased compared with that in normal skin. And the expression level of matrix metalloproteinases-12 in human melanoma was closely related to the clinical status of invasion and metastasis. In vivo research proved that decreased matrix metalloproteinases-12 expression in melanoma cells can suppress invasion ability of melanoma cells. We also confirmed that matrix metalloproteinases-12 was regulated by CD147 in melanoma.Taken together, the present study illustrated the expression pattern of matrix metalloproteinases-12 in melanoma and its invasion promotion effect in melanoma cells, which would provide cluues for understanding the role of matrix metalloproteinases-12 in the melanoma.