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Article

Downregulation of MMP-9 Enhances the Anti-Migratory Effect of Cyclophosphamide in MDA-MB-231 and MCF-7 Breast Cancer Cell Lines

Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
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Author to whom correspondence should be addressed.
Academic Editor: Michael Welsh
Int. J. Mol. Sci. 2021, 22(23), 12783; https://doi.org/10.3390/ijms222312783
Received: 4 November 2021 / Revised: 18 November 2021 / Accepted: 23 November 2021 / Published: 26 November 2021
(This article belongs to the Collection Feature Papers in Molecular Oncology)
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). View Full-Text
Keywords: MMP-9; CP; CK19; breast cancer; metastasis MMP-9; CP; CK19; breast cancer; metastasis
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MDPI and ACS Style

Izdebska, M.; Zielińska, W.; Krajewski, A.; Hałas-Wiśniewska, M.; Mikołajczyk, K.; Gagat, M.; Grzanka, A. Downregulation of MMP-9 Enhances the Anti-Migratory Effect of Cyclophosphamide in MDA-MB-231 and MCF-7 Breast Cancer Cell Lines. Int. J. Mol. Sci. 2021, 22, 12783. https://doi.org/10.3390/ijms222312783

AMA Style

Izdebska M, Zielińska W, Krajewski A, Hałas-Wiśniewska M, Mikołajczyk K, Gagat M, Grzanka A. Downregulation of MMP-9 Enhances the Anti-Migratory Effect of Cyclophosphamide in MDA-MB-231 and MCF-7 Breast Cancer Cell Lines. International Journal of Molecular Sciences. 2021; 22(23):12783. https://doi.org/10.3390/ijms222312783

Chicago/Turabian Style

Izdebska, Magdalena, Wioletta Zielińska, Adrian Krajewski, Marta Hałas-Wiśniewska, Klaudia Mikołajczyk, Maciej Gagat, and Alina Grzanka. 2021. "Downregulation of MMP-9 Enhances the Anti-Migratory Effect of Cyclophosphamide in MDA-MB-231 and MCF-7 Breast Cancer Cell Lines" International Journal of Molecular Sciences 22, no. 23: 12783. https://doi.org/10.3390/ijms222312783

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