Abstract
Metastasis is one of the most urgent issues in breast cancer patients. One of the factors necessary in the migration process is the remodeling of the extracellular matrix (ECM). Metalloproteinases (MMPs) can break down the elements of the ECM, which facilitates cell movement. Many highly aggressive tumors are characterized by high levels of MMPs. In the case of breast cancer, the association between MMP-9 and the migration potential and invasiveness of cells has been demonstrated. In addition, reports indicating increased migration of breast cancer cells after the administration of the commonly used cytostatic cyclophosphamide (CP) are particularly disturbing. Hence, our research aimed to assess the effect of CP treatment on MDA-MB-231 and MCF-7 cells and how this response is influenced by the downregulation of the MMP-9 level. The obtained results suggest that CP causes a decrease in the survival of breast cancer cells of various invasiveness, and the downregulation of MMP-9 enhances this effect, mainly by inducing apoptosis. Moreover, in the group of MMP-9 siRNA-transfected CP-treated cells, a more severe reduction in invasion and migration of cells of both lines was observed, as indicated by the migration and invasion transwell assays and Wound healing assay. Hence, we suggest that CP alone may not result in satisfactory therapeutic effects. On the other hand, the use of combination therapy targeting MMP-9, together with the CP, could improve the effectiveness of the treatment. Additionally, we confirmed a relationship between the levels of MMP-9 and cytokeratin 19 (CK19).
Highlights
One of the most important problems of cancer patients is metastasis
We wanted to investigate how reduced matrix (ECM). Metalloproteinases (MMPs)-9 expression affects the response of breast cancer cells (MDA-MB-231 and MCF-7) to CP treatment and whether there is a correlation between MMP-9 and cytokeratin 19 (CK19)
Densitometric analysis of the bands reflecting protein levels obtained by Western blot indicated a decrease in MMP-9 level in cells of the MCF-7 and MDA-MB-231 lines transfected with MMP-9 siRNA compared to cells transfected with control siRNA and non-transfected cells
Summary
One of the most important problems of cancer patients is metastasis. It contributes to almost 66.7% of cancer mortality [1]. MMPs enzymatic activity correlates with the stage of cancer, increased invasiveness, and lower survival rate. These factors emphasize the value of MMPs in the prognosis and monitoring of the effectiveness of cancer treatment [9,10]. MMP-9 is crucial in metastasis due to the high potential for ECM degradation (various substrates: gelatin types I and V, collagen types IV and V, fibronectin). Our study aimed to investigate how changes in the expression level and enzymatic activity of MMPs affect the proliferative and migratory capacity and metastatic potential of breast cancer cells. We wanted to investigate how reduced MMP-9 expression affects the response of breast cancer cells (MDA-MB-231 and MCF-7) to CP treatment and whether there is a correlation between MMP-9 and CK19
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 call
