Anti-?4 integrin antibodies enhance migratory and invasive abilities of human colon adenocarcinoma cells and their MMP-2 expression

Daémi, N; Thomasset, Nicole; Lissitzky, Jean‐Claude; Dumortier, Jérôme; Jacquier, Marie-France; Pourreyron, Céline; Rousselle, Patricia; Chayvialle, Jean‐Alain; Rémy, Lionel

doi:10.1002/(sici)1097-0215(20000315)85:6<850::aid-ijc19>3.0.co;2-b

Cited by 28 publications

(17 citation statements)

References 23 publications

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“…Thus, loss of c0634 and the absence of hemidesmosome formation may provide a more motile and invasive SCC tumor. This notion is supported by the fact that blocking antibodies to 14 can result in stimulation of cell migration and an increase in MMP-2 activity (Daemi et al, 2000). Finally, transfection of the f4 subunit into a neoplastic keratinocyte cell line failed to restore the differentiation capacity or proliferation properties, suggesting that x6134 is not required for these properties in SCC (Jones et al, 1996).…”

Section: L5j31mentioning

confidence: 96%

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Adhesive Mechanisms Regulating Invasion and Metastasis in Oral Cancer

Ziober

Silverman

Kramer

2001

Critical Reviews in Oral Biology & Medicine

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It is the relentless invasion and growth into surrounding tissue that characterize oral squamous cell carcinoma. Metastasis is perhaps the most challenging and important aspect of cancer progression, in that it generally signifies limited survival and ineffective therapy. Inherent in metastasis is invasion, the process by which cells infiltrate into adjacent tissues, degrading basement membranes and extracellular matrix and disrupting tissue architecture and sometimes organ function. The factors that regulate these processes are complex and likely involve loss of the controls that are normally in place in physiologic tissue modeling. Adhesion receptors and their ligands are important in modulating not only invasion of oral squamous cell carcinoma cells but also their survival and proliferation. Normal oral mucosal epithelial cells use integrins to maintain their anchorage to the basement membrane, whereas the formation of stratifying cell layers depends on the formation of intercellular adhesions mediated by cadherins. The process of squamous cell carcinoma invasion and dissemination requires active cell migration through the extracellular matrix with the simultaneous remodeling of intercellular adhesions. Integrins are clearly important in the invasive process, whereas intercellular adhesion receptors restrain invasion and promote a more differentiated phenotype.

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Section: L5j31mentioning

confidence: 96%

“…Substantial evidence has attributed loss of and/or mutations in p53 in the pathogenesis of SCC (Pavelic and Gluckman, 1997). Finally, recent work has indicated that the (4 subunit of cx6,B4 can stimulate specific signals responsible for cell motility, expression of MMP-2, and tumor invasion (Daemi et al, 2000).…”

Section: L5j31mentioning

confidence: 99%

Adhesive Mechanisms Regulating Invasion and Metastasis in Oral Cancer

Ziober

Silverman

Kramer

2001

Critical Reviews in Oral Biology & Medicine

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“…Protease inhibitors were from Sigma (St. Louis, MO). 35 S-methionine was provided by Amersham (Les Ulis, France). Laminin-1 and vitronectin were prepared according to Timpl et al 26 and Yatogho et al, 27 respectively.…”

Section: Reagentsmentioning

confidence: 99%

“…30 In some experiments, cells were cultured for 48 hours in the presence of increasing concentrations of the furin inhibitor dec-RVKRcmk. Cells were then metabolically labeled with 1 Ci/ml 35 S-methionine for 2 hours and tested for migration in the presence of phorbol 12-myristate 13-acetate (PMA). Following incubation at 37°C, cells on the upper surface of the membrane were wiped with a cotton swab.…”

Section: Cell Migrationmentioning

confidence: 99%

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Inhibition of Proprotein Convertases Enhances Cell Migration and Metastases Development of Human Colon Carcinoma Cells in a Rat Model

Nejjari

Berthet

Rigot

et al. 2004

The American Journal of Pathology

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Although proprotein convertases are involved in tumor development, nothing is known about their role in metastatic dissemination. To investigate the involvement of convertase inhibition, we used human colon carcinoma cells overexpressing ␣1-antitrypsin Portland (␣1-PDX, PDX39P cells), a potent convertase inhibitor. We previously reported that these cells bear uncleaved integrin ␣ subunits and display an altered attachment to vitronectin that is correlated with defects in the intracellular signaling pathways activated by ␣v␤5 integrin ligation. In this study, we demonstrate that the inhibition of proprotein convertase activity either by overexpression of ␣1-PDX or with the synthetic inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethylketone (dec-RVKR-cmk) led to a significant increase in cell migration supported by the ␣v␤5 integrin. A collagen gel invasion assay showed that PDX39P cells also displayed an invasive ability, contrary to control cells. Moreover, when injected to immunosuppressed newborn rats, PDX39P cells were highly invasive, as they induce 10 times more metastases than mock-transfected cells. In addition, the aggressiveness of PDX39P cells can be greatly reduced by a function-blocking monoclonal antibody (mAb) against the ␣v subunit. It thus seems that inhibition of proprotein convertases enhances the in vivo invasiveness of colon tumor cells likely due to an increase in cell migration mediated by ␣v integrins. The acquisition of cell motility and the capacity to invade basement matrix membranes and adjacent tissues play a central role in the complex multi-step process of metastasis. Cell migration is the result of dynamic interactions between the cell, the extracellular matrix (ECM), and the cytoskeleton. Integrins connect the ECM proteins outside to the actin cytoskeleton within the cell, allowing the traction required for cell migration. 1,2 Integrins also play a crucial role in signal transduction events that control anchorage-independent growth and survival of tumor cells (for reviews, see references [3][4][5] ). Therefore, these adhesion molecules play a pivotal role in tumor cell invasion and metastasis. [5][6][7] Integrins are heterodimeric proteins composed by the non-covalent association of ␣ and ␤ subunits. Some integrin ␣ chains undergo a post-translational cleavage in their extracellular domain by furin and PC5A, two proprotein convertases (PCs) of the subtilisin/kexin family. 8,9 The role of this cleavage in integrin function remains unclear. Arguably, this post-translational processing of the ␣ chain is not required for ligand binding, 10 -12 but is essential for the signaling function of ␣6␤1 and ␣v␤5 integrins. 10,13 Moreover, recent data suggest that the ␣6 subunit cleavage might be linked to the differentiation state of lens cells. 14 PCs are responsible for the biological activation of a variety of precursor proteins, including pro-hormones and their receptors and adhesion molecules. They are ubiquitously expressed and are involved in many physiological and pathological processes. ...

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New insights into the roles of matrix metalloproteinases in colorectal cancer development and progression

Leeman

Curran

Murray

2003

The Journal of Pathology

144

111

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This review outlines new concepts that are emerging for the functions of matrix metalloproteinases in colorectal cancer development and progression. The two main concepts that will be discussed are the role of matrix metalloproteinases in the early stages of colorectal tumour development and the functional mechanisms by which matrix metalloproteinases contribute to colorectal tumour invasion and metastasis. The matrix metalloproteinases are a group of enzymes, which have been best characterized for their ability to degrade extracellular matrix proteins and thus they have been extensively studied in tumour invasion. It is now becoming recognized that the matrix metalloproteinases have key roles in a variety of biological processes that are distinct from their well-defined role in matrix degradation. This group of enzymes has been shown to interact with a broad range of non-matrix proteins including growth factors and their receptors, mediators of apoptosis, and cell adhesion molecules. The elucidation of novel biological roles for the matrix metalloproteinases also challenges the current predominant concept of matrix metalloproteinases as enzymes only involved in matrix degradation. Recent studies have shown that several matrix metalloproteinases, especially matrilysin (MMP-7), interact with the specific molecular genetic and signalling pathways involved in colorectal cancer development. In particular, matrilysin is activated at an early stage of colorectal tumourigenesis by the beta-catenin signalling pathway. Furthermore, studies are now elucidating specific mechanisms by which individual matrix metalloproteinases, especially membrane-type matrix metalloproteinases, interact with specific cell adhesion molecules and cytoskeletal proteins and thus contribute dynamically to colorectal tumour invasion.

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Anti-?4 integrin antibodies enhance migratory and invasive abilities of human colon adenocarcinoma cells and their MMP-2 expression

Cited by 28 publications

References 23 publications

Adhesive Mechanisms Regulating Invasion and Metastasis in Oral Cancer

Adhesive Mechanisms Regulating Invasion and Metastasis in Oral Cancer

Inhibition of Proprotein Convertases Enhances Cell Migration and Metastases Development of Human Colon Carcinoma Cells in a Rat Model

New insights into the roles of matrix metalloproteinases in colorectal cancer development and progression

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