Stimulation of extracellular matrix components in the normal brain by invading glioma cells

Knott, Jo C. A.; Mahesparan, Rupavathana; Garcia-Cabrera, Inmaculada; Tysnes, Berit Bølge; Edvardsen, Klaus; Ness, Gro Oddveig; Mörk, Sverre; Lund‐Johansen, Morten; Bjerkvig, Rolf

doi:10.1002/(sici)1097-0215(19980316)75:6<864::aid-ijc8>3.0.co;2-t

Cited by 85 publications

(49 citation statements)

References 37 publications

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“…20 This observation was confirmed and extended to other central nervous system tumors (astrocytoma, meningioma, and neuroblastoma). 21 In addition, as reported in this study and by others, 11,22 glioblastoma cell lines express ␣6 integrin subunit. The only exception is, to our knowledge, the U87 cell line.…”

Section: Discussionsupporting

confidence: 81%

“…47,48 It is known that in normal brain tissue, laminin is associated with blood vessels and is overexpressed when brain is confronted to glioma cells. 22 In addition, in vitro studies have demonstrated that laminin-111 is one of the most permissive substrates for adhesion and migration of glioma cells. [25][26][27] Using both time-lapse video-microscopy and haptotaxis assays, we show here that expression of the integrin ␣6␤1 noticeably enhanced glioblastoma cells migration on laminin-111.…”

Section: Discussionmentioning

confidence: 99%

“…In glioblastoma biopsies, laminin-111 is highly expressed on tumor blood vessels, but also within the brain tumor as punctuate deposits and at the tumor invasion front. 22 In vitro, glioma cells can both secrete laminin-111 and induce its expression in normal brain tissue. [22][23][24] Moreover, laminin-111 is one of the most permissive substrates for adhesion and migration of glioma cells in vitro.…”

mentioning

confidence: 99%

“…22 In vitro, glioma cells can both secrete laminin-111 and induce its expression in normal brain tissue. [22][23][24] Moreover, laminin-111 is one of the most permissive substrates for adhesion and migration of glioma cells in vitro. [25][26][27] Additionally, over laminin-111, migrating glioma cells are protected from apoptosis.…”

mentioning

confidence: 99%

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Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells

Delamarre

Taboubi

Mathieu

et al. 2009

The American Journal of Pathology

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The integrin ␣6␤1 and its main ligand laminin-111 are overexpressed in glioblastoma, as compared with normal brain tissue, suggesting they may be involved in glioblastoma malignancy. To address this question, we stably expressed the ␣6 integrin subunit in the U87 cell line via retroviral-mediated gene transfer. We show that cell surface expression of the ␣6␤1 integrin led to dramatic changes in tumor U87 cell behavior, both in vitro and in vivo. Nude mice receiving either subcutaneous or intracerebral inoculation of ␣6␤1-expressing cells developed substantially more voluminous tumors than mice injected with control cells. The difference in tumor growth was associated with a marked increase in vascularization in response to ␣6␤1 integrin expression and may also be related to changes in the balance between cell proliferation and survival. Indeed, expression of ␣6␤1 enhanced proliferation and decreased apoptosis of U87 cells both in the tumor and in vitro. Additionally, we demonstrate that ␣6␤1 is implicated in glioblastoma cell migration and invasion and that laminin-111 might mediate dissemination of ␣6␤1-positive cells in vivo. Our results highlight for the first time the considerable role of the integrin ␣6␤1 in glioma progression. Malignant brain tumors have an increasing incidence in both children and adults. In adults, the most common type of primary brain tumor, malignant glioma, is considered as one of the deadliest of human cancers. Despite recent advances in both diagnostic modalities and therapeutic strategies, the 5-year survival rate of less than 3% in patients with glioblastoma is among the lowest for all cancers.1 Patients with the most malignant histopathological subtype, glioblastoma, carry the worst prognosis, with median survival rate of less than 1 year, despite aggressive surgery associated with adjuvant radiotherapy and chemotherapy. 1 Glioblastoma are characterized by rapidly dividing cells, high degree of vascularity, invasion into normal brain tissue, and an intense resistance to death-inducing stimuli.2,3 Since integrins, the major family of extracellular matrix (ECM) receptors, are involved in these events, they are one of the most promising molecules to consider for a targeted therapy.Integrins are cell surface transmembrane ␣␤ heterodimers that recognize specific ECM ligands. The combination of ␣ and ␤ subunits, leading to the formation of at least 24 receptors, determines the ligand specificity. 4 Glioblastoma commonly displays enhanced expression of several integrins along with their ECM ligands: ␣v␤3 and ␣v␤5 (tenascin and vitronectin receptors), ␣5␤1 (fibronectin receptor), ␣2␤1 (collagens receptor), and ␣3␤1, ␣6␤4, and ␣6␤1 (laminins receptors).5 Numerous studies have focused on the ␣v integrin family. The integrins ␣v␤3 and ␣v␤5 are markers of glioblastoma malignancy 6 and influence a variety of processes in glioblastoma progression in vivo, including proliferation, apoptosis, and angiogenesis.7 Furthermore, cilengitide, an ␣v␤3 and ␣v␤5 integrins antagonist, extends mouse surviv...

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells

Delamarre

Taboubi

Mathieu

et al. 2009

The American Journal of Pathology

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“…Some HSPGs, e.g., syndecan-2 were reported to be increased in brain tumors (Theocharis et al 2010). Laminin, collagen and fibronectin were also shown to be expressed by normal brain tissue bordering with glioma cells in spheroids (Knott et al 1998). In addition, some of these molecules are also expressed by cells of highly aggressive gliomas.…”

Section: Vasculature-associated Ecm Molecules Expressed By Gliomasmentioning

confidence: 98%

Extracellular Matrix Microenvironment in Glioma Progression

Wiranowska¹,

Rojiani²

2011

Glioma - Exploring Its Biology and Practical Relevance

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Integrin involvement in glioblastoma multiforme: Possible regulation by NF-?B

2000

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Glioblastoma multiforme (GBM) is the most malignant astroglial-derived tumors which has the propensity to aggressively infiltrate normal regions of the brain surrounding the tumor. The interaction of tumor cells with the extracellular matrix (ECM) is an integral step in the process of tumorigenesis and may play a role in the local invasion of the GBM cells. Our study investigated the role of the nuclear transcription factor NF-kappaB on GBM integrin expression and cell attachment. Our results show that treatment of GBM cell lines, SNB-19 and T98G with PMA, an inducer of NF-kappaB, increased the expression of fibronectin and vitronectin genes. Accordingly, ectopic over-expression of NFkappaB subunits in GBM cells elevated the levels of fibronectin gene expression, providing direct evidence for a regulatory role for NF-kappaB in ECM protein production. Cell attachment to the ECM proteins including fibronectin, vitronectin and laminin was increased in GBM and normal astrocytic cells. Interestingly, treatment of cells with PMA augmented attachment of SNB-19 and T98G cells to fibronectin and vitronectin, however it had no effect on attachment of normal astrocytes. Addition of the tripeptide arginine-glycine-asparatic acid (RGD), the recognition site for many integrins, significantly inhibited SNB-19 and T98G cell attachment to fibronectin and vitronectin. Finally, activation of NFkappaB upon treatment of SNB cells with PMA led to an increase in the levels of mRNA for the beta3 and the alphav integrin subunits. Collectively, these data demonstrate a possible role for NF-kappaB in glioma cell attachment.

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Stimulation of extracellular matrix components in the normal brain by invading glioma cells

Cited by 85 publications

References 37 publications

Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells

Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells

Extracellular Matrix Microenvironment in Glioma Progression

Integrin involvement in glioblastoma multiforme: Possible regulation by NF-?B

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