Abstract
In cancer progression, proteolytic enzymes like serine proteases and metalloproteinases degrade the basement membrane enabling the tumor cells to invade the adjacent tissues. Thus, invasion and metastasis are augmented by these enzymes. Simultaneous silencing of uPA and MMP9 in breast cancer cells decreased the wound healing, migratory, invasive and adhesive capacity of the cells. After simultaneous down regulation, cells were seen to be arrested in the cell cycle. There was a remarkable increase in the expression of cell to cell adhesion molecule E–cadherin, and decrease in Vimentin and Snail expression. In addition, there was a significant decrease in the expression of the stem cell marker Oct-4. In the breast tumor samples it has been observed that, tumors, expressing higher level of uPA and MMP9, express less amount of E–cadherin. It has also been observed that few tumors also show, Vimentin positive in the ductal epithelial area. Thus, our model can help for checking the aggressive tumor invasion by blocking of uPA and MMP9. Our present observations also give the concept of the presence of aggressive epithelial cells with mesenchymal nature in the tumor micro-environment, altering the expression of EMT genes.
Highlights
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer related deaths in women worldwide
After transfecting the breast cancer cells MDA-MB-231, T47D and ZR-75-1 with siRNA against urokinase plasminogen activator (uPA) and MMP9, transcript levels have been checked in the respective cells
A significant reduction of the expression of uPA and MMP9 were observed in the MDA-MB-231 cells (80%) in comparison to the T47D and ZR-75-1 cells (Supplementary Fig. 1, Supplementary Table S1)
Summary
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer related deaths in women worldwide. Metastasis of the cancer starts at the primary site of the tumor by invading and degrading the basement membrane and extracellular matrix (ECM)[2]. This invasive nature of the tumor cells is necessary for the metastasis. In the process of cancer progression, tumor cells which starts to dissociate from the primary tumor invade into the neighboring tissue and transmit through the blood vessels and form colonies at a secondary site[3] is related to cellular behavior ‘Epithelial-to-Mesenchymal Transition’ (EMT). In the ovarian and breast cancer, uPA and PAI-1 have been found to be expressed at a high level[10]. Higher uPA level indicates reduced patient survival and act as prognostic marker along with PAI-111,12
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
