SIKVAV, a Laminin α1-Derived Peptide, Interacts with Integrins and Increases Protease Activity of a Human Salivary Gland Adenoid Cystic Carcinoma Cell Line through the ERK 1/2 Signaling Pathway

Freitas, Vanessa M.; Vilas-Boas, Vanessa F.; Pimenta, Daniel C.; Loureiro, Vania; Juliano, María A.; Carvalho, Márcia Regina; Pinheiro, João de Jesus Viana; Camargo, Antônio Carlos Martins de; Moriscot, Anselmo Sigari; Hoffman, Matthew P.; Jaeger, Ruy Gastaldoni

doi:10.2353/ajpath.2007.051264

Cited by 71 publications

(90 citation statements)

References 66 publications

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“…45 During the present study, we observed, by zymographic analysis, that U87 cells secrete both MMP-2 and MMP-9 (data not shown). However, in contrast to the result from adenoid cystic carcinoma, 46 the expression of the integrin ␣6␤1 did not affected MMP secretion (data not shown).…”

Section: Discussioncontrasting

confidence: 62%

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: Discussioncontrasting

confidence: 62%

Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells

Delamarre

Taboubi

Mathieu

et al. 2009

The American Journal of Pathology

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“…MAP family kinases are likely to play vital role in signaling processes that regulate several MMPs, including MMP-9 by modulating several transcription factors [28]. Laminin derived peptides have been reported to enhance MMP-9 secretion via ERK pathway in human salivary gland adenoid cystic carcinoma [29]. Laminin-1 treatment was found to enhance ERK phosphorylation and nuclear translocation in MCF-7 cells in our study.…”

Section: Discussionsupporting

confidence: 58%

Extracellular Matrix Protein Laminin Induces Matrix Metalloproteinase-9 in Human Breast Cancer Cell Line MCF-7

Pal

Moulik

Dutta

et al. 2014

Cancer Microenvironment

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Studies on interaction of tumor cells with extracellular matrix (ECM) components showed increased extracellular protease activity mediated by the family of matrix metalloproteinases (MMPs). Here we studied the effect of human breast cancer cell line MCF-7-laminin (LM) interaction on MMPs and the underlying signaling pathways. Culturing of MCF-7 cells on LM coated surface upregulated MMP-9 expression as well as reduced tissue inhibitor of metalloproteinases-1 (TIMP-1) expression. LM induced MMP-9 expression is abrogated by the blockade of α 2 integrin. Inhibitor studies indicate possible involvement of phosphatidyl-inositol-3-kinase (PI3K), extracellular signal regulated kinase (ERK) and nuclear factor-kappaB (NF-κB) in LM induced signaling. LM treatment also enhanced phosphorylation of FAK (focal adhesion kinase), PI3K, ERK; nuclear translocation of ERK, pERK, NF-κB and cell migration. Our findings indicate that, binding of MCF-7 cells to LM, possibly via α 2 β 1 integrin, induces signaling involving FAK, PI3K, ERK, NF-κB followed by upregulation of MMP-9 and cell migration.

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“…7 Among MMPs, MMP-2 and MMP-9 are particularly upregulated in SACC and many other malignant tumors and contribute to the invasion of tumor cells by degrading the ECM. [34][35][36] Our previous study found that the expression of MMP-2 and MMP-9 was associated with EMMPRIN expression in SACC. 11 In the present study, we found that knockdown of EMMPRIN expression in SACC-83 cells reduced the secretion of MMP-2 and MMP-9, thus inhibiting the PNI ability of SACC-83 cells through the reconstituted basement membrane in vitro.…”

Section: Do Not Distributementioning

confidence: 99%

EMMPRIN silencing inhibits proliferation and perineural invasion of human salivary adenoid cystic carcinoma cells in vitro and in vivo

Yang

Zhang

et al. 2012

Cancer Biology & Therapy

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Salivary adenoid cystic carcinoma (SACC) is a frequent subtype of salivary gland malignancy, and it has an important biological behavior for perineural invasion (PNI). Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that is involved in the invasive property of many malignancies by stimulating matrix metalloproteinase (MMP) expression. The present study was designed to investigate the role and possible mechanism of EMMPRIN in the PNI of SACC using RNA interference (RNAi) technology. We found that silencing of EMMPRIN expression in the human SACC cell line (SACC-83) suppressed the cell proliferation, adhesion, MMP-2 and MMP-9 secretion, and PNI activity in vitro. EMMPRIN silencing also inhibited the tumor growth and K i -67 labeled proliferation index in vivo. Using tumor PNI models in nude mice, EMMPRIN silencing inhibited the infiltration, swelling and functional loss of the affected sciatic nerves, as well as the expression of MMP-2 and MMP-9. These results demonstrate that EMMPRIN participates in the PNI of SACC cells by mediating the expression of MMP-2 and MMP-9. Our findings suggest that EMMPRIN is a potential target for anti-PNI treatment in SACC.

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SIKVAV, a Laminin α1-Derived Peptide, Interacts with Integrins and Increases Protease Activity of a Human Salivary Gland Adenoid Cystic Carcinoma Cell Line through the ERK 1/2 Signaling Pathway

Cited by 71 publications

References 66 publications

Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells

Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells

Extracellular Matrix Protein Laminin Induces Matrix Metalloproteinase-9 in Human Breast Cancer Cell Line MCF-7

EMMPRIN silencing inhibits proliferation and perineural invasion of human salivary adenoid cystic carcinoma cells in vitro and in vivo

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