| Tumor cell invasion and metastasis to secondary sites are complex, multistep processes including cell detachment from the primary site, migration through lymph or blood vessels, adhesion to cellular and extracellular matrix elements of the organs involved, proteolytic degradation of matrix proteins and cell proliferation. Several above processes involved proteolysis of the extracellular matrix and tissue remodeling. Matrix metalloproteinases (MMPs) comprise a family of enzymes whose main function is the degradation of extracellular matrix, and have been implicated in tumor progression. It was documented that type IV collagenase with two subtypes of 72kDa/MMP-2 and 92kDa/MMP-9 plays an important role in tumor invasion and metastasis, based on the mechanism of proteolytic degradation of collagen IV in basement membrane by which malignant tumor initiates its invasion and spread.It has been demonstrated that natural and synthetic inhibitors of type IV collagenase such as TIMPs, BB94 have reduced the metastasis of murine Lewis lung carcinoma and tumor neovascularization . These finding suggested that blocking the function of type IV collagenase represents a useful strategy in cancer therapy and prevention of metastasis.One possible method to inhibit specifically the function of a protein is to express intracellular antibody (intrabody) combining site that can block the function or prevent the expression of the targeted molecule. Intracellular antibodies are novel agents that can be used to study or to alter the function of specific cellular proteins. Intracellular scFv has been used as a novel approach to gene therapy to inhibit a variety of HIV proteins, resulting in ablating the replication of HIV virus in T cells. Many groups have used scFv to abrogate the expression of oncoproteins. Thus, scFv can achieve effectively functional knock-out of target oncoproteins. Based on this concept, intracellular antibodies against type IV collagenase may have therapeutic use against tumor...
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