| Matrix Metalloproteinase (MMP2), in particular MMP-2, induced in the adjacent normal stroma are necessary for the degradation of extracellular matrix (ECM) essential for cancer metastasis. The breaking of immune tolerance of MMP-2 combined low-dose chemotherapy should be an approach to treatment cancer metastasis by active immunity and chemotherapy. For test this concept, we constructed a plasmid DNA encoding chicken homologous MMP-2 (c-MMP-2), combination therapy with low-dose cisplatin (DDP). In this experiment, lung metastasis of murine colon Aden carcinoma (C26) in tumor model were established in 6-to 8- weeks of age female BALB/c mice, and then treated with 0.9% NaCL solution (NS), DDP, c-MMP-2, or c-MMP-2 combined DDP. We found that both c-MMP-2 and low-dose DDP treatment individually resulted in cancer metastasis inhibition to certain extent. Remarkably, combination therapy resulted in significantly decreased the number of lung surface metastasis nodules, markedly decreased lungs of weight, and prolongation of the survival of tumor-bearing. Immunohistochemical staining of the tumors demonstrated an obviously decreased number of blood vessels in combination treatment group compared with other groups, whereas terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) showed a significantly increased in mice of tumor cells apoptosis in combination treatment group. Autoantibodies against MMP-2 in serum of mice immunized with c-MMP-2 and c-MMP-2 combined DDP are found by enzyme-linked immunospot assay (ELISA), c-MMP-2 group and c-MMP-2combined DDP group alone is apparently increased in IgGl and IgG2b. At the same time, adoptive immunity also demonstrated combination therapy resulted in obvious prolongation survival of mice-bearing. Thus the combination of c-MMP-2 and low-dose DDP resulted an additive effect of antimetastasis. The observation may provide an important strategy for treatment cancer metastasis.
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