Comparative expression pattern of Matrix-Metalloproteinases in human glioblastoma cell-lines and primary cultures

Abstract

BackgroundGlioblastomas (GBM), the most frequent malignant brain tumors in adults, are characterized by an aggressive local growth pattern and highly invasive tumor cells. This invasion is facilitated by expression of matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases. They mediate the degradation of protein components of the extracellular matrix. Twenty-three family members are known. Elevated levels of several of them have been reported in GBM. GBM cell-lines are used for in vitro studies of cell migration and invasion. Therefore, it is essential to know their MMP expression patterns. Only limited data for some of the cell-lines are published, yet. To fill the gaps in our knowledge would help to choose suitable model systems for analysis of regulation and function of MMPs during GBM tumorigenesis, cell migration and invasion.FindingsWe analysed MMP-1, -8, -9, -10, -11, -13, -17, -19, -20, -21, -23, -24, -26, -27, and MMP-28 expression in seven GBM cell-lines (SNB-19, GaMG, U251, U87, U373, U343, U138) and in four primary cell cultures by semiquantitative RT-PCR, followed changes in the MMP expression pattern with increasing passages of cell culture and examined the influence of TNF-α and TGF-β1 stimulation on the expression of selected MMPs in U251 and U373 cells.MMP-13, -17, -19 and -24 were expressed by all analyzed cell-lines, whereas MMP-20 and MMP-21 were not expressed by any of them. The other MMPs showed variable expression, which was dependent on passage number. Primary cells displayed a similar MMP-expression pattern as the cell-lines. In U251 and U373 cells expression of MMP-9 and MMP-19 was stimulated by TNF-α. MMP-1 mRNA expression was significantly increased in U373 cells, but not in U251 cells by this cytokine. Whereas TGF-β1 had no impact on MMP expression in U251 cells, it significantly induced MMP-11 and MMP-24 expression in U373 cells.ConclusionsLiterature-data and our own results suggest that the expression pattern of MMPs is highly variable, dependent on the cell-line and the cell-culture conditions used and that also regulation of MMP expression by cytokines is cell-line dependent. This is of high impact for the transfer of cell-culture experiments to clinical implementation.

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

“…Very recently one study suggested that significant elevation of MMP28 levels in glioblastoma patients may predict unfavorable overall survival (12). High expressions of MMP11 and 19 seen in all the meningiomas in this study are consistent with the findings of previous reports using RT-PCR, western blotting and immunohistochemistry which indicated that they correlated with the WHO-grading of human malignant gliomas (11). Indeed, MMP19 has also been reported to be a facilitator of invasion in gliomas (33).…”

“…This further confirms the notion that benign meningiomas express some of these MMPs as they have potential to invade like malignant gliomas. In contrast, MMP20 was not detected in any of the meningiomas, similar to previous findings with various cancers including de novo glioblastoma multiforme (9) and 7 established GBM cell lines (11).…”

“…The expression of some MMPs has been well studied in gliomas (8)(9)(10)(11)(12) and meningiomas (13)(14)(15)(16)(17)(18)(19) particularly in relation to invasion or recurrence. Closely related to the MMPs is the ADAM (a disintegrin and metalloproteinase) family which has also been implicated in cancer, particularly via ADAMmediated activation of EGFR signalling (20).…”

EphrinA1 Is Released in Three Forms from Cancer Cells by Matrix Metalloproteases

“…Additionally, expression of collagenases, such as MMP-1 and MMP-13, is deregulated in various cancers (9). MMP-1 expression has been documented to occur in GBM cells (4,21), and increased expression correlates with increased tumor grade (58,71) and tumorigenicity (52), and decreased survival in GBM patients (71). Moreover, increased MMP-13 production in glioma cells in response to various stimuli leads to an increase in migration and invasion (43).…”

The mechanism of action of the scorpion toxin, chlorotoxin, a bioinformatics approach

“…Furthermore, immunohistochemical technique showed the localisation of MMP2 and MMP9 in only glioma cells and its blood vessels (Sawaya et al, 1996;Ramachandran et al, 2017). MMP2 was highly expressed in GBM tissue samples as well as all transformed cell lines but not in healthy brain tissues (Deshane et al, 2003;Kargiotis et al, 2008;Hagemann et al, 2010;Rahme et al, 2015).…”