Genetic polymorphisms of matrix metalloproteinases and their inhibitors in potentially malignant and malignant lesions of the head and neck

被引:61
作者
Chaudhary, Ajay Kumar [1 ,2 ]
Singh, Mamta [1 ]
Bharti, Alok C. [3 ]
Asotra, Kamlesh [4 ]
Sundaram, Shanthy [2 ]
Mehrotra, Ravi [1 ]
机构
[1] MLN Med Coll, Dept Pathol, Allahabad, Uttar Pradesh, India
[2] Univ Allahabad, Ctr Biotechnol, Allahabad 211002, Uttar Pradesh, India
[3] ICPO, Div Mol Oncol, Noida, India
[4] Univ Calif, Tobacco Related Dis Res Program, Off President Oakland, Oakland, CA USA
关键词
SQUAMOUS-CELL CARCINOMA; SINGLE-NUCLEOTIDE POLYMORPHISM; METASTATIC BREAST-CANCER; HUMAN TISSUE INHIBITOR; GROUP TRIAL E2196; MALE ARECA USERS; PHASE-I; PROMOTER POLYMORPHISM; TUMOR PROGRESSION; CERVICAL-CANCER;
D O I
10.1186/1423-0127-17-10
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Matrix metalloproteinases ( MMPs) are a family of zinc-dependent proteinases that are capable of cleaving all extra cellular matrix (ECM) substrates. Degradation of matrix is a key event in progression, invasion and metastasis of potentially malignant and malignant lesions of the head and neck. It might have an important polymorphic association at the promoter regions of several MMPs such as MMP-1 (-1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A), MMP-9 (-1562 C/T) and TIMP-2 (-418 G/C or C/C). Tissue inhibitors of metalloproteinases (TIMPs) are naturally occurring inhibitors of MMPs, which inhibit the activity of MMPs and control the breakdown of ECM. Currently, many MMP inhibitors (MMPIs) are under development for treating different malignancies. Useful markers associated with molecular aggressiveness might have a role in prognostication of malignancies and to better recognize patient groups that need more antagonistic treatment options. Furthermore, the introduction of novel prognostic markers may also promote exclusively new treatment possibilities, and there is an obvious need to identify markers that could be used as selection criteria for novel therapies. The objective of this review is to discuss the molecular functions and polymorphic association of MMPs and TIMPs and the possible therapeutic aspects of these proteinases in potentially malignant and malignant head and neck lesions. So far, no promising drug target therapy has been developed for MMPs in the lesions of this region. In conclusion, further research is required for the development of their potential diagnostic and therapeutic possibilities.
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页数:13
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