Pancreatic Cancer Cells Induce TIMP-1 but Not MMP Production in Pancreatic Stelllate Cells
Abstracts
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Pancreatic adenocarcinoma is surrounded by an intense desmoplastic reaction. Pancreatic stellate cells (PSC) are known to produce components of this extracellular matrix; however, their ability to regulate matrix resorption is unknown. We hypothesized that pancreatic cancer cells induce pancreatic stellate cells to produce matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP). Methods. Serum-free media from Panc-1 cells was passed through a sep pak, lyophilized, and reconstituted. Control media (serum-free) was subjected to the exact same procedures. Rodent pancretic stellate cells (105) were exposed to Panc-1 conditioned media for 24 hours. Total RNA was isolated, and gene induction for MMP-2, TIMP-1, and TIMP-2 were determined. MMP-2 and 9 protein were measured in the supernatant by gelatin zymography. Results. Pancreatic stellate cell MMP-2 and TIMP-2 mRNA were not increased with exposure to cancer cell media (data not shown) while TIMP-1 mRNA increased 4 fold (Figure). MMP-2 and 9 protein were not increased in response to Panc-1 conditioned media. Conclusions. Panc-1 cancer cell media induces pancreatic stellate cell TIMP-1 while MMP-2 and 9 and TIMP-2 are not increased. The selective induction of TIMP-1 may contribute to the intense desmoplastic reaction that surrounds pancreatic cancers. |
