c-Myb regulates matrix metalloproteinases 1/9, and cathepsin D: implications for matrix-dependent breast cancer cell invasion and metastasis

<p>Abstract</p> <p>Background</p> <p>The c-Myb transcription factor is essential for the maintenance of stem-progenitor cells in bone marrow, colon epithelia, and neurogenic niches. c-Myb malfunction contributes to several types of malignancies including breast cancer. However, the function of c-Myb in the metastatic spread of breast tumors remains unexplored. In this study, we report a novel role of c-Myb in the control of specific proteases that regulate the matrix-dependent invasion of breast cancer cells.</p> <p>Results</p> <p>Ectopically expressed c-Myb enhanced migration and ability of human MDA-MB-231 and mouse 4T1 mammary cancer cells to invade Matrigel but not the collagen I matrix <it>in vitro</it>. c-Myb strongly increased the expression/activity of cathepsin D and matrix metalloproteinase (MMP) 9 and significantly downregulated MMP1. The gene coding for cathepsin D was suggested as the c-Myb-responsive gene and downstream effector of the migration-promoting function of c-Myb. Finally, we demonstrated that c-Myb delayed the growth of mammary tumors in BALB/c mice and affected the metastatic potential of breast cancer cells in an organ-specific manner.</p> <p>Conclusions</p> <p>This study identified c-Myb as a matrix-dependent regulator of invasive behavior of breast cancer cells.</p

Granulation tissue enriched by aspirin and omega-3 fatty acids in healing experimental periodontal lesion

Aims. Granulation tissue (GT) and specialized proresolving mediators such as lipoxins and resolvins are key elements in the successful resolution of periodontitis. Aspirin triggered lipoxins and resolvins are even more powerful than their natural analogues. Their biosynthesis can be accelerated by omega3 fatty acids. The aim of this study was to evaluate the use of GT enriched by aspirin and omega‑3 fatty acids during the surgical treatment of periodontitis in an experimental animal model (rabbit). Methods. In each of 24 rabbits, two experimental periodontal defects were created. In total, 47 defects were treated with open flap debridement and one of three procedures: (1) GT extracted and soaked with aspirin and omega‑3 fatty acids (ASA+OMEGA3 group); (2) GT soaked with saline (PLACEBO group); or (3) GT left untreated (CONTROL group). Then, the GT was replaced in situ. Primary evaluated criteria were the probing pocket depth (PPD) and the clinical at‑ tachment level (CAL). Necropsies were harvested 2, 6, and 12 weeks after surgery. The samples were used for histological and molecular biological assessment. Results. A trend of greater PPD and CAL in the ASA+OMEGA3 group was observed at 6 weeks. However, there was no significant difference between them. During the observation period, tissue levels of FGF‑7, IL1β and TIMP1 showed a statistically significant decrease (P&lt;0.05). For the other variables, the ASA+OMEGA3 group was comparable with the PLACEBO and CONTROL groups. Conclusion. This experiment did not demonstrate the superiority of the proposed approach. However, the enriched granulation tissue did not impair healing outcomes