Tumor cell-produced matrix metalloproteinase 9 (MMP-9) drives malignant progression and metastasis of basal-like triple negative breast cancer

Abstract

Matrix metalloproteinases (MMPs) have been implicated in diverse roles in breast cancer development and progression. While many of the different MMPs expressed in breast cancer are produced by stromal cells MMP-9 is produced mainly by the tumor cells themselves. To date, the functional role of tumor cell-produced MMP-9 has remained unclear. Here, we show that human breast cancer cell-produced MMP-9 is specifically required for invasion in cell culture and for pulmonary metastasis in a mouse orthotopic model of basal-like breast cancer. We also find that tumor cell-produced MMP-9 promotes tumor vascularization with only modest impact on primary tumor growth, and that silencing of MMP-9 expression in tumor cells leads to an altered transcriptional program consistent with reversion to a less malignant phenotype. MMP-9 is most highly expressed in human basal-like and triple negative tumors, where our data suggest that it contributes to metastatic progression. Our results suggest that MMP9 may offer a target for anti-metastatic therapies for basal-like triple negative breast cancers, a poor prognosis subtype with few available molecularly targeted therapeutic options.

Effect of Ephedra foeminea active compounds on cell viability and actin structures in cancer cell lines

“…Part of the activity of invadopodia in invading extracellular membranes is due to localized proteolytic activity of MMPs (Yamaguchi, 2012), involved in tumor metastasis (Foda and Zucker, 2001). In particular, MMP9 was found to be produced mainly by the MDA-MB-231 tumor cells and to significantly contribute to metastatic progression (Mehner et al, 2014). The fact that treatment with the E. foeminea ethanol extract leads to a marked increase in MMP9 expression suggests that this extract may indeed induce formation of invadopodia-like structures.…”

“…qPCR was used to determine the gene transcription of matrix metallopeptidase 9 (MMP9) in treated and non-treated MDA-MB-231 cells as described above. Expression of MMPs characterizes cells undergoing induction of invadopodia, whereas MMP9 is produced mainly by the MDA-MB-231 cells and contributes to metastatic progression (Mehner et al, 2014). The qPCR was performed using components supplied in the KAPA SYBR FAST qPCR kits (Kapa Biosystems, USA) and genes specific primers.…”

New Insights into the Occurrence of Matrix Metalloproteases -2 and -9 in a Cohort of Breast Cancer Patients and Proteomic Correlations

“…Indeed both collagenolytic enzymes have been individually correlated with breast cancer progression [12] and with tumor vascularization, invasion and metastasis, differentiation and proliferation [13]. We initially aimed to verify the occurrence of gelatinase activities in 30 tissue samples of breast carcinomas vs the adjacent non-affected tissues.…”

FNC, a Novel Nucleoside Analogue, Blocks Invasion of Aggressive Non-Hodgkin Lymphoma Cell Lines Via Inhibition of the Wnt/β-Catenin Signaling Pathway

“…With the deepening of the mechanism research, promoting the invasion and metastasis of tumor cells involves in various factors, including the continuous activation of Wnt/β-catenin signaling pathway (Yuan et al, 2012;Rao et al, 2013), abnormal regulation of E-cadherin signal mechanism (Bae et al, 2013), abnormal degradation of cell matrix in tumor microenvironment and excessive release of angiogenine (Mehner et al, 2014;Saarelainen et al, 2014). They interact with each other to enhance the invasion and metastasis of tumor cells.…”