Tumor cell expression of MMP3 as a prognostic factor for poor survival in pancreatic, pulmonary, and mammary carcinoma.

Breast, lung, and pancreatic cancers collectively represent one third of all diagnosed tumors and are responsible for almost 40% of overall cancer mortality. Despite improvements in current treatments, efforts to develop more specific therapeutic options are warranted. Here we identify matrix metalloproteinase 3 (MMP3) as a potential target within all three of these tumor types. MMP3 has previously been shown to induce expression of Rac1b, a tumorigenic splice isoform of Rac1. In this study we find that MMP3 and Rac1b proteins are both strongly expressed by the tumor cells of all three tumor types and that expression of MMP3 protein is prognostic of poor survival in pancreatic cancer patients. We also find that MMP3 gene expression can serve as a prognostic marker for patient survival in breast and lung cancer. These results suggest an oncogenic MMP3-Rac1b signaling axis as a driver of tumor progression in three common poor prognosis tumor types, further suggesting that new therapies to target these pathways could have substantial therapeutic benefit.