Bradykinin induces matrix metalloproteinase‐9 expression and cell migration through a PKC‐δ‐dependent ERK/Elk‐1 pathway in astrocytes

Hsieh, Hsi‐Lung; Wu, Cheng‐Ying; Yang, Che‐Hua

doi:10.1002/glia.20637

Cited by 98 publications

(153 citation statements)

References 52 publications

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“…This was not surprising, as the same was described by Hsieh et al (31), showing that BK induced MMP9 expression and enhanced cell migration via a PKC-delta-dependent ERK/ Elk-1 pathway in astrocytes. This pathway (32,33) and/or alternative possibilities, such as induction of reactive oxygen species (ROS)-dependent pathways, were also shown in brain astrocytes (34).…”

Section: Discussionsupporting

confidence: 77%

Glioblastoma‐mesenchymal stem cell communication modulates expression patterns of kinin receptors: Possible involvement of bradykinin in information flow

et al. 2015

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The most aggressive subtype of brain tumors is glioma WHO grade IV, the glioblastoma (GBM). The present work aims to elucidate the role of kinin receptors in interactions between GBM cells and mesenchymal stem cells (MSC). The GBM cell line U87-MG was stably transfected to express dsRed protein, single cell cloned, expanded, and cultured with MSC, both in the direct co-cultures (DC) and indirect co-cultures (IC) at equal cell number ratio for 72 h. Up-and down-regulation of matrix metalloproteases (MMP)29 expression in U87-MG and MSC cells, respectively, in direct coculture points to possible MSC participation in tumor invasion. MMP9 expression is in line with significantly increased expression of kinin B1 (B1R) and B2 receptor (B2R) in U87-MG cells and their decreased levels in MSC, as confirmed by quantitative assessment using flow cytometric analysis. Similarly, in indirect cultures (IC), lacking the contact between GBM and MSC cells, an increase of B1 and B2 receptor expression was again noted in U87-MG cells, and no significant changes in kinin receptors in MSC was observed. Functionality of kinin-B1 and B2 receptors was evidenced by stimulation of intracellular calcium fluxes by their respective agonists, des-Arg9-bradykinin (DBK) and bradykinin (BK). Moreover, BK showed a feedback control on kinin receptor expression in mono-cultures, direct and indirect co-cultures. The treatment with BK resulted in down-regulation of B1 and B2 receptors in MSC, with simultaneous upregulation of these receptors in U87-MG cells, suggesting that functions of BK in information flow between these cells is important for tumor progression and invasion. V C International Society for Advancement of CytometryKey terms Bradykinin; kinin-B1 receptor; kinin-B2 receptor; glioblastoma; bone-marrow mesenchymal stem cells; direct and indirect cell co-culture GLIOMAS, although classified as a rare neoplastic disease, are still the most frequent brain tumors and their most malignant form (WHO stage IV astrocytoma). Glioblastoma (GBM) has an average postoperative survival of only 14.6 or 12.1 months when treated with radio-and chemo-therapy (temozolomide) or with radiotherapy alone, respectively (1). The major characteristic of these tumors is the high infiltration rate of single cells, the so called "guerrilla" cells into the brain parenchyma, even several cm away from the bulk tumor mass. These cells are hard to target by conventional therapies. In view of that, the development of novel therapeutic strategies for successful GBM treatment targeting tumor invasiveness has turned into an aim of priority.

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Section: Discussionsupporting

confidence: 77%

Glioblastoma‐mesenchymal stem cell communication modulates expression patterns of kinin receptors: Possible involvement of bradykinin in information flow

et al. 2015

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“…Hepatocyte growth factor (HGF) increased the rate of invasion, Elk-1 phosphorylation (pElk-1) and MMP-9 secretion in the human hepatoma cell line, HepG2 (37). Elk-1 is a transcription factor known to induce the expression of the MMP-2 and MMP-9 gene by binding to the promoter region of the MMP-2 and MMP-9 gene after phosphorylation (38,39). Therefore, SLPI-siRNA was transfected to SNU638 cells to regulate MMP-2 and MMP-9 by SLPI.…”

Section: Discussionmentioning

confidence: 99%

Secretory leukocyte protease inhibitor is associated with MMP-2 and MMP-9 to promote migration and invasion in SNU638 gastric cancer cells

Choi

Jeong²,

Wang³

et al. 2011

Int J Mol Med

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Abstract. Secretory leukocyte protease inhibitor (SLPI) protects tissue from proteases, and promotes cell proliferation and healing during inflammatory response. SLPI is also overexpressed in gastric, lung and ovarian cancers, which accelerates the metastasis of cancer cells. Matrix metalloproteinases-2, -9 (MMP-2 and MMP-9) are overexpressed in high metastatic cancers, and promote the migration of cancer cells through collagen degradation. SLPI and MMP-2, -9 are critical factors in stimulating the metastatic processes but there are no reports of a direct correlation between these molecules. Therefore, this study examined the role of SLPI related to MMP-2 and MMP-9 using two gastric cancer cell lines, such as characterized non-metastatic SNU484 and highly metastatic SNU638 cells. SLPI, MMP-2 and MMP-9 mRNA and protein expression were higher in SNU638 cells than in SNU484 cells. In addition, the rate of cell migration and invasion was higher in the SNU638 cells than in SNU484 cells. Interestingly, after treatment with SLPI, the rate of migration and invasion was higher in the SNU484 cells than in the positive control (PC) SNU484 cells. The rate of migration was also higher in the SNU638 cells after SLPI treatment than in the SNU638 cells (PC) but the invasion rate was not changed. The expression and secretion of MMP-2 and MMP-9 as well the rate of cell migration and invasion were significantly lower in SLPIsiRNA transfected SNU638 cells (si-SLPI/SNU638) but higher in SLPI-treated SNU484 cells (SNU484 + SLPI). Strong Elk-1 phosphorylation was detected in SNU484 + SLPI and SNU638 cells but was barely detectable in SNU484 and si-SLPI/SNU638 cells. These results show that SLPI promotes the metastasis of SNU638 gastric cancer cells by increasing MMP-2 and MMP-9 expression through Elk-1 signaling, indicating its role as a signaling molecule not a protease inhibitor. IntroductionThe metastatic cascade of cancer cells is viewed as a series of sequential and interrelated steps, which include the following: epithelial-mesenchymal transition (EMT), degradation of the basement membrane; dissociation of tumor cells from the primary site; invasion of the neighboring tissue; intravasation into the blood and lymph vessels; transport through the vessels; extravasation from the vessels; and proliferation at a distant site. Among these processes, tumor cells invading the neighboring tissue after degrading the basement membrane is a major development (1).Secretory leukocyte protease inhibitor (SLPI) is an 11.7-kDa cystein-rich protein and an epithelial cell product found in saliva, seminal plasma and in the cervical, nasal, and bronchial mucus. SLPI inhibits the serine protease activity, such as chymotrypsin, trypsin, pancreatic elastase, cathepsin G, mast cell chymase (2). Recently, SLPI was reported to be an anti-inflammatory factor that contributes at the early inflammatory response in odontoblasts (3). In addition, SLPI was reported to play a role not only in protecting the tissues from the protease (4) but also in promoting wou...

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“…23) On the other hand, Hsieh et al reported that bradykinin, which is degraded by ACE, induced the MMP-9 expression and cell migration in astrocytes. 24) Thus, it is speculated that captopril may promote and prolong the isoprenaline-induced MMP-9 expressions through increasing cardiac b-adrenergic receptor or through inhibiting the degradation of bradykinin. Further study is needed to clarify the mechanism by which captopril promotes the isoprenaline-induced MMP-9 expression.…”

Section: Discussionmentioning

confidence: 99%

Effects of Captopril and Telmisartan on Matrix Metalloproteinase-2 and -9 Expressions and Development of Left Ventricular Fibrosis Induced by Isoprenaline in Rats

Okada

Kosaka

Hoshino

et al. 2010

Biological & Pharmaceutical Bulletin

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Bradykinin induces matrix metalloproteinase‐9 expression and cell migration through a PKC‐δ‐dependent ERK/Elk‐1 pathway in astrocytes

Cited by 98 publications

References 52 publications

Glioblastoma‐mesenchymal stem cell communication modulates expression patterns of kinin receptors: Possible involvement of bradykinin in information flow

Glioblastoma‐mesenchymal stem cell communication modulates expression patterns of kinin receptors: Possible involvement of bradykinin in information flow

Secretory leukocyte protease inhibitor is associated with MMP-2 and MMP-9 to promote migration and invasion in SNU638 gastric cancer cells

Effects of Captopril and Telmisartan on Matrix Metalloproteinase-2 and -9 Expressions and Development of Left Ventricular Fibrosis Induced by Isoprenaline in Rats

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