In cancer, the extracellular matrix is extensively remodeled during chronic inflammation, thus affecting cell transcription, differentiation, migration and cell-cell interactions. Matrix metalloproteinases can degrade the extracellular matrix of tumor tissues and take important roles in disease progression. Numerous efforts to develop cancer treatments targeting matrix metalloproteinases have failed in clinical trials owing to the ineffectiveness and toxicity of the applied inhibitors. In this study, we investigated the potential of targeting matrix metalloproteinases and oncolytic virus combination in cancer therapy. We found that MMP3 expression was upregulated in various cancers and MMP3 expression in the tumor cells, but not in other tissues, was important for tumor growth and metastasis. Single treatment of colon cancer with multiple MMP3 inhibitors was not effective in mice. Nevertheless, the therapeutic effect of MMP3 was greatly improved by combination with an oncolytic virus. A potential mechanism of MMP3 in regulating tumor cell proliferation and invasion was mediated via Erk1/2 an NF-κB signaling. This study reveals that MMP3 is a promising target and the combined treatment with oncolytic virus is a potential strategy for cancer therapy.

在癌症中，细胞外基质在慢性炎症期间被广泛重塑，从而影响细胞转录、分化、迁移和细胞间相互作用。基质金属蛋白酶可以降解肿瘤组织的细胞外基质，在疾病进展中发挥重要作用。由于所应用的抑制剂的无效性和毒性，许多开发靶向基质金属蛋白酶的癌症治疗的努力在临床试验中都失败了。在这项研究中，我们研究了靶向基质金属蛋白酶和溶瘤病毒组合在癌症治疗中的潜力。我们发现 MMP3 表达在各种癌症中上调，肿瘤细胞中的 MMP3 表达对肿瘤生长和转移很重要，但在其他组织中则不然。用多种 MMP3 抑制剂单次治疗结肠癌对小鼠无效。然而，通过与溶瘤病毒的组合，MMP3的治疗效果大大提高。MMP3 调节肿瘤细胞增殖和侵袭的潜在机制是通过 Erk1/2 和 NF-κB 信号传导介导的。该研究表明，MMP3 是一个很有前景的靶点，与溶瘤病毒联合治疗是癌症治疗的潜在策略。