Cells activated for wound repair have the potential to direct collective invasion of an epithelium

Bleaken, Brigid M.; Menko, A. Sue; Walker, James B.

doi:10.1091/mbc.e15-09-0615

Cited by 25 publications

(31 citation statements)

References 61 publications

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“…The area of the invasive front denotes as “tumor buds”, where groups of cancer cells are signaled to move collectively from their original site and invade a surrounding matrix environment[ 16 – 17 ]. We chose the area of the invasive front from each primary tissue, which was employed for immunohistochemical analysis.…”

Section: Methodsmentioning

confidence: 99%

Cytokeratin-14 contributes to collective invasion of salivary adenoid cystic carcinoma

Gao

Cao

et al. 2017

PLoS ONE

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Collective invasion of cells plays a fundamental role in tissue growth, wound healing, immune response and cancer metastasis. This paper aimed to investigate cytokeratin-14 (CK14) expression and analyze its association with collective invasion in the invasive front of salivary adenoid cystic carcinoma (SACC) to uncover the role of collective invasion in SACC. Here, in the clinical data of 121 patients with SACC, the positive expression of CK14 was observed in 35/121(28.93%) of the invasive front of SACC. CK14 expression in the invasive front, local regional recurrence and distant metastasis were independent and significant prognostic factors in SACC patients. Then, we found that in an ex vivo 3D culture assay, CK14 siRNA receded the collective invasion, and in 2D monolayer culture, CK14 overexpression induced a collective SACC cell migration. These data indicated that the presence of characterized CK14+ cells in the invasive front of SACC promoted collective cell invasion of SACC and may be a biomarker of SACC with a worse prognosis.

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Section: Methodsmentioning

confidence: 99%

Cytokeratin-14 contributes to collective invasion of salivary adenoid cystic carcinoma

Gao

Cao

et al. 2017

PLoS ONE

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“…Vimentin is required for the function of this mesenchymal leader cell population in directing the collective migration of the injured epithelium to close the wound ( Walker et al , 2010 ; Menko et al , 2014a ). Furthermore, we have found that when these cells are activated by wounding, they are also conferred with the ability to invade, a phenotype that is also dependent on vimentin ( Bleaken et al , 2016 ). This finding is consistent with other studies showing that vimentin is required for an invasive-cell phenotype ( Satelli and Li, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

In wound repair vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype

Walker

Bleaken

Romisher

et al. 2018

MBoC

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Following injury, mesenchymal repair cells are activated to function as leader cells that modulate wound healing. These cells have the potential to differentiate to myofibroblasts, resulting in fibrosis and scarring. The signals underlying these differing pathways are complex and incompletely understood. The ex vivo mock cataract surgery cultures are an attractive model with which to address this question. With this model we study, concurrently, the mechanisms that control mesenchymal leader cell function in injury repair within their native microenvironment and the signals that induce this same cell population to acquire a myofibroblast phenotype when these cells encounter the environment of the adjacent tissue culture platform. Here we show that on injury, the cytoskeletal protein vimentin is released into the extracellular space, binds to the cell surface of the mesenchymal leader cells located at the wound edge in the native matrix environment, and supports wound closure. In profibrotic environments, the extracellular vimentin pool also links specifically to the mesenchymal leader cells and has an essential role in signaling their fate change to a myofibroblast. These findings suggest a novel role for extracellular, cell-surface–associated vimentin in mediating repair-cell function in wound repair and in transitioning these cells to a myofibroblast phenotype.

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“…LEcs, functionally coupled to one another, regulate the majority of the homeostatic functions of the lens (34,35). Following cataract surgery residual aberrant epithelial cells in injured tissues trigger a dysregulated repair process, characterized by cell migration towards the posterior capsule and ECM deposition, which results in secondary visual loss (36). TGF-β2 is considered the most important cytokine responsible for this ectopic wound healing process (37).…”

Section: Discussionmentioning

confidence: 99%

The role of focal adhesion kinase in transforming growth factor-β2 induced migration of human lens epithelial cells

Liu

et al. 2018

Int J Mol Med

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The migration of lens epithelial cells towards the posterior capsule is a key event in the development of posterior capsule opacification (PCO). Accumulating evidence has described crosstalk between growth factors and adhesive signaling pathways in wound healing and cell migration. The aim of the present study was to elucidate an aberrant transforming growth factor (TGF)-β2 signaling pathway that regulated the migration of lens epithelial cells in the pathological context of PCO. The expression of fibronectin, focal adhesion kinase (FAK) and phosphorylated (p)-FAK in HLE-B3 cells following TGF-β2 treatment was determined by western blot analysis and the expression of integrin α5β1 was detected by flow cytometry. Cell migration capacity was measured by wound healing and Transwell assays in the presence of 1,2,4,5-tetraaminobenzene tetrahydrochloride, a selective FAK inhibitor, fibronectin small interfering RNA interference, arginylglycylaspartic acid peptides or α5β1-integrin neutralizing antibodies. The 1,2,4,5-tetraaminobenzene tetrahydrochloride was administered daily to 16 rabbits following cataract surgery. Fibronectin and TGF-β expression were increased in the PCO group, demonstrated by immunofluorescence assays. PCO grading was conducted by slit-lamp biomicroscopy and evaluation of posterior capsule opacification software. It was observed that TGF-β2 promoted HLE-B3 cell migration and upregulated fibronectin expression, which was followed by an increased phosphorylation of FAK. In addition, TGF-β2 treatment and fibronectin surface coating significantly increased cell migration and FAK activation, which was inhibited by disrupting fibronectin-integrin α5β1 interaction with the arginylglycylaspartic acid peptide, α5β1-integrin neutralizing antibody or fibronectin depletion. Finally, suppression of FAK signaling by its inhibitor significantly decreased cell migration in vitro and attenuated PCO development in vivo. In summary, TGF-β2 was indicated to promote the migration of lens epithelial cells through the TGF-β2/fibronectin/integrin/FAK axis. Inhibition of FAK activity decreased TGF-β2-mediated cell migration in vitro and improved the symptoms of PCO in a rabbit model.

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Cells activated for wound repair have the potential to direct collective invasion of an epithelium

Cited by 25 publications

References 61 publications

Cytokeratin-14 contributes to collective invasion of salivary adenoid cystic carcinoma

Cytokeratin-14 contributes to collective invasion of salivary adenoid cystic carcinoma

In wound repair vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype

The role of focal adhesion kinase in transforming growth factor-β2 induced migration of human lens epithelial cells

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