Project description:Response of pancreas cancer cells to treatment with recombinant MMP3 Cells were treated with 100U/ml MMP3 for 4 days, then isolated for RNA. The submitted experiments represent two different experiments performed at different times
Project description:Response of mouse mammary epithelial cells to treatment with MMP3 Cells were untreated (d1 control) or treated with MMP3 for 1-4 days (d1-4 MMP3), or washed and then allowed to recover for three additional days (d5-7 recover) then isolated for RNA.
Project description:Response of pancreas cancer cells to treatment with recombinant MMP3 Cells were treated with 100U/ml MMP3 for 4 days, then isolated for RNA. The submitted experiments represent two different experiments performed at different times
Project description:Seventy percent of women with ovarian cancer develop resistance to cisplatin, contributing to persistently high mortality rates. Understanding the mechanisms behind this resistance is crucial for developing improved therapies. Matrix metalloproteinase 3 (MMP3) is elevated in ovarian cancer patients, but its role in cisplatin resistance remains underexplored. We observed significantly higher MMP3 protein and mRNA levels in cisplatin-resistant high-grade serous ovarian cancer (HGSOC) cells compared to cisplatin-sensitive cells, with further increases following cisplatin treatment. Kaplan‒Meier analysis indicated that patients with lower MMP3 levels have better survival outcomes. MMP3 knockdown via siRNA reduced cell viability, proliferation, and invasion, effects enhanced by cisplatin; however, a chemical MMP3 inhibitor did not replicate these effects. To better understand MMP3’s role, we conducted RNA sequencing to analyze gene expression changes and used immunoprecipitation with mass spectrometry to identify MMP3-interacting proteins, making this the first study to explore this in cisplatin-resistant ovarian cancer. Surprisingly, multiple injections of liposomal MMP3-siRNA increased tumor size in a mouse model, while combining MMP3-siRNA with cisplatin reduced tumor growth. These findings highlight MMP3’s complex role in cisplatin resistance and raise concerns about its targeting in vivo.
Project description:Cancer metastasis remains an important unsolved problem. Matrix metalloproteinases (MMPs) have been shown to promote cancer cell transformation, migration, invasion, and metastasis through alteration of the extracellular microenvironment, and alter intracellular signaling and genome status. In addition, recent studies have shown intracellular and intranuclear localization, as well as roles of MMPs. In the present study, we examined gene expression signatures of high- and low-metastatic mouse colon cancer cells, and found that Mmp3 was expressed at the highest level in the high-metastatic cells. Profound nuclear localization of Mmps was found in primary explant sites as well as in areas of metastasis in lungs. In addition to the native 50-kDa Mmp3, a short 25-kDa PEX domain and active Mmp3 dimer were found in metastatic cancer cells, indicating novel roles for these forms. Knockdown of Mmp3 attenuated cancer cell viability, migration, and invasion in vitro, along with metastasis in an in vivo transplantation model, as well as cancer cell migration and invasion. These findings suggest that MMPs including intracellular, short, and dimerized forms are involved with malignant progression of cancer, thus they may be suitable as biomarkers and therapeutic targets.
Project description:Effect of induction of MMP3 expression in CCSP-rtTA/tet-MMP3 transgenic mice, fed doxycycline for 14 weeks We used microarrays to detail the global programme of gene expression following MMP3 expression Transgenic mice (CCSPrt-TA/tet-MMP3 or CCSPrtTA control mice) were fed doxycycline from week 6 to week 20, then lungs were removed, formalin fixed, and embedded in paraffin. Sections were sliced from the paraffin blocks for RNA extraction.
Project description:Effect of induction of MMP3 expression in CCSP-rtTA/tet-MMP3 transgenic mice, fed doxycycline for 14 weeks We used microarrays to detail the global programme of gene expression following MMP3 expression