EGF stimulates glioblastoma metastasis by induction of matrix metalloproteinase-9 in an EGFR-dependent mechanism

Chen, Xing-Chen; Wei, Xiao‐Hong; Guan, Jian; Song, Hong; Chen, Duo

doi:10.18632/oncotarget.19622

Cited by 33 publications

(19 citation statements)

References 44 publications

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“…Moreover, inhibition of GBM cells by EGFR is associated with anti-angiogenic and pro-apoptotic effects on the tumor [72]. It has been reported that coactivation of EGF and EGFR drives tumor metastasis via PI3K/AKT-dependent pathways [73]. Targeting FAK/STAT3 sensitizes gliomas to the anti-EGFR agent gefitinib and alkylating agent temozolomide in human gliomas [74].…”

Section: Discussionmentioning

confidence: 99%

Monocarboxylate Transporter 4 Regulates Glioblastoma Motility and Monocyte Binding Ability

Lai

Lin

Liu

et al. 2020

Cancers

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Glioblastoma (GBM) is characterized by severe hypoxic and acidic stress in an abnormal microenvironment. Monocarboxylate transporter (MCT)4, a pH-regulating protein, plays an important role in pH homeostasis of the glycolytic metabolic pathways in cancer cells. The present study showed that GBM exposure to hypoxic conditions increased MCT4 expression. We further analyzed the glioma patient database and found that MCT4 was significantly overexpressed in patients with GBM, and the MCT4 levels positively correlated with the clinico-pathological grades of gliomas. We further found that MCT4 knockdown abolished the hypoxia-enhanced of GBM cell motility and monocyte adhesion. However, the overexpression of MCT4 promoted GBM cell migration and monocyte adhesion activity. Our results also revealed that MCT4-regulated GBM cell motility and monocyte adhesion are mediated by activation of the serine/threonine-specific protein kinase (AKT), focal adhesion kinase (FAK), and epidermal growth factor receptor (EGFR) signaling pathways. Moreover, hypoxia mediated the acetylated signal transducer and activator of transcription (STAT)3 expression and regulated the transcriptional activity of hypoxia inducible factor (HIF)-1α in GBM cell lines. In a GBM mouse model, MCT4 was significantly increased in the tumor necrotic tissues. These findings raise the possibility for the development of novel therapeutic strategies targeting MCT4.

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Section: Discussionmentioning

confidence: 99%

Monocarboxylate Transporter 4 Regulates Glioblastoma Motility and Monocyte Binding Ability

Lai

Lin

Liu

et al. 2020

Cancers

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“…Equipped with this functional background, tumor cells alternate with macrophages along extra cellular matrix fibers until they reach blood vessels where macrophages facilitate the entry of tumor cells across the vessel wall [ 138 , 139 ]. Moreover, it is known that EGF plays a role in the metastasis of glioblastoma by induction of matrix metalloproteinase-9 in an EGFR-dependent mechanism [ 140 ].…”

Section: Discussionmentioning

confidence: 99%

Role of Macrophages in Brain Tumor Growth and Progression

Guadagno

Presta

Maisano

et al. 2018

IJMS

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The role of macrophages in the growth and the progression of tumors has been extensively studied in recent years. A large body of data demonstrates that macrophage polarization plays an essential role in the growth and progression of brain tumors, such as gliomas, meningiomas, and medulloblastomas. The brain neoplasm cells have the ability to influence the polarization state of the tumor associated macrophages. In turn, innate immunity cells have a decisive role through regulation of the acquired immune response, but also through humoral cross-talking with cancer cells in the tumor microenvironment. Neoangiogenesis, which is an essential element in glial tumor progression, is even regulated by the tumor associated macrophages, whose activity is linked to other factors, such as hypoxia. In addition, macrophages play a decisive role in establishing the entry into the bloodstream of cancer cells. As is well known, the latter phenomenon is also present in brain tumors, even if they only rarely metastasize. Looking ahead in the future, we can imagine that characterizing the relationships between tumor and tumor associated macrophage, as well as the study of circulating tumor cells, could give us useful tools in prognostic evaluation and therapy. More generally, the study of innate immunity in brain tumors can boost the development of new forms of immunotherapy.

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“…MMP-9 and EGFR are both present in the cerebrospinal-fluid (CSF) of patients and their levels decline after tumour resection. MMP-9 transcription is stimulated by EGFR and EGFRvIII in glioblastoma, with signalling pathways involved such as PI3K/AKT (PKB), STAT3/5, NFk-B, ERK and Sonic hedgehog (SHH) [44][45][46]. MMP-9 can cleave several ECM components, preferentially type IV collagen, gelatine, and elastin; but also, regulates cell-ECM interactions: MMP-9 is able to act on cell motility via direct cleavage of CD44, a surface glycoprotein involved in cell-ECM interactions via binding to several ECM ligands, mainly hyaluronic acid.…”

Section: Mmp-9 In Glioblastoma Progressionmentioning

confidence: 99%

Extracellular proteolysis in glioblastoma progression and therapeutics

Quesnel

Karagiannis

Filippou

2020

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Gliomas encompass highly invasive primary central nervous system (CNS) tumours of glial cell origin with an often-poor clinical prognosis. Of all gliomas, glioblastoma is the most aggressive form of primary brain cancer. Current treatments in glioblastoma are insufficient due to the invasive nature of brain tumour cells, which typically results in local tumour recurrence following treatment. The latter represents the most important cause of mortality in glioblastoma and underscores the necessity for an in-depth understanding of the underlying mechanisms. Interestingly, increased synthesis and secretion of several proteolytic enzymes within the tumour microenvironment, such as matrix metalloproteinases, lysosomal proteases, cathepsins and kallikreins for extracellularmatrix component degradation may play a major role in the aforementioned glioblastoma invasion mechanisms. These proteolytic networks are key players in establishing and maintaining a tumour microenvironment that promotes tumour cell survival, proliferation, and migration. Indeed, the targeted inhibition of these proteolytic enzymes has been a promisingly useful therapeutic strategy for glioblastoma management in both preclinical and clinical development. We hereby summarize current advances on the biology of the glioblastoma tumour microenvironment, with a particular emphasis on the role of proteolytic enzyme families in glioblastoma invasion and progression, as well as on their subsequent prognostic value as biomarkers and their therapeutic targeting in the era of precision medicine.

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EGF stimulates glioblastoma metastasis by induction of matrix metalloproteinase-9 in an EGFR-dependent mechanism

Cited by 33 publications

References 44 publications

Monocarboxylate Transporter 4 Regulates Glioblastoma Motility and Monocyte Binding Ability

Monocarboxylate Transporter 4 Regulates Glioblastoma Motility and Monocyte Binding Ability

Role of Macrophages in Brain Tumor Growth and Progression

Extracellular proteolysis in glioblastoma progression and therapeutics

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