Cathepsin G Induces Cell Aggregation of Human Breast Cancer MCF-7 Cells via a 2-Step Mechanism: Catalytic Site-Independent Binding to the Cell Surface and Enzymatic Activity-Dependent Induction of the Cell Aggregation

Morimoto-Kamata, Riyo; Mizoguchi, Sei-ichiro; Ichisugi, Takeo; Yui, Satoru

doi:10.1155/2012/456462

Cited by 31 publications

(38 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Treatment of cells with OSI‐906, axitinib and sunitinib blocked cell detachment by >50%, as compared with vehicle treatment, while vandetanib and pazopanib, and sorafenib yielded moderate and weak inhibition of CG‐induced cell detachment, respectively. Notably, while CG enzymatic activity is essential for the induction of cell aggregation, none of these six compounds affected this activity (Fig. c).…”

Section: Resultsmentioning

confidence: 97%

“…SDS‐PAGE and subsequent western blotting analyses were performed as previously described . Cell lysates were prepared by solubilizing cells in radio‐immunoprecipitation assay (RIPA) buffer (50 mM Tris‐HCl [pH 7.5] containing 150 mM NaCl, 1% NP‐40, and 0.1% sodium deoxycholate) supplemented with protease‐inhibitor and phosphatase‐inhibitor cocktails (Sigma).…”

Section: Methodsmentioning

confidence: 99%

“…Because tumor‐cell aggregates can cause emboli in blood and lymphatic vessels, followed by intravascular and secondary growth in target organs, these findings suggest that CG could function as a metastasis‐promoting factor. With respect to the molecular mechanism of CG‐induced cell aggregation, we have shown that this process occurs in a CG enzymatic activity‐dependent and protease‐activated receptors (PARs)‐independent manner . Furthermore, CG‐induced cell aggregation does not solely involve the degradation of ECM, such as fibronectin .…”

mentioning

confidence: 99%

See 2 more Smart Citations

Insulin‐like growth factor‐1 signaling is responsible for cathepsin G‐induced aggregation of breast cancer MCF‐7 cells

Morimoto-Kamata

Yui

2017

Cancer Science

Self Cite

View full text Add to dashboard Cite

Cathepsin G (CG), a neutrophil serine protease, induces cell migration and multicellular aggregation of human breast cancer MCF‐7 cells in a process that is dependent on E‐cadherin and CG enzymatic activity. While these tumor cell aggregates can cause tumor emboli that could represent intravascular growth and extravasation into the surrounding tissues, resulting in metastasis, the molecular mechanism underlying this process remains poorly characterized. In this study, we aimed to identify the signaling pathway that is triggered during CG‐mediated stimulation of cell aggregation. Screening of a library of compounds containing approximately 90 molecular‐targeting drugs revealed that this process was suppressed by the insulin‐like growth factor‐1 (IGF‐1) receptor (IGF‐1R)‐specific kinase inhibitor OSI‐906, as well as the multikinase inhibitors axitinib and sunitinib. Antibody array analysis, which is capable of detecting tyrosine phosphorylation of 49 distinct receptor tyrosine kinases, and the results of immunoprecipitation studies indicated that IGF‐1R is phosphorylated in response to CG treatment. Notably, IGF‐1R neutralization via treatment with a specific antibody or silencing of IGF‐1R expression through siRNA transfection suppressed cell aggregation. Furthermore, CG treatment of MCF‐7 cells resulted in increased release of IGF‐1 into the medium for 24 h, while antibody‐mediated IGF‐1 neutralization partially prevented CG‐induced cell aggregation. These results demonstrate that autocrine IGF‐1 signaling is partly responsible for the cell aggregation induced by CG.

show abstract

Section: Resultsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Insulin‐like growth factor‐1 signaling is responsible for cathepsin G‐induced aggregation of breast cancer MCF‐7 cells

Morimoto-Kamata

Yui

2017

Cancer Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…5 Furthermore, the physiological cues, which modulate the adherent capacity of the tumour cell within its microenvironment remain poorly understood. 9 Cells in the body are typically surrounded by an extracellular matrix and are in direct physical contact with surrounding cells, conditions that are poorly replicated within 2D culture. Growing evidence suggests 3D spheroid culture to provide a more accurate representative model of in vivo tissues than traditional 2D monolayers.…”

Section: Introductionmentioning

confidence: 99%

Development of an hydrophobic fluoro-silica surface for studying homotypic cancer cell aggregation–disaggregation as a single dynamic process in vitro

et al. 2014

View full text Add to dashboard Cite

a Under normal conditions the detachment of anchorage-dependant cells from their extracellular matrix typically induces programmed cell death which is mediated through a pathway referred to as anoikis.However, a resistance to anoikis in cancer enables the migration of cells from the primary tumour and the establishment of aggressive metastatic disease. Although cancer cell aggregation is known to be an important mechanism within anoikis resistance, research into the underlying mechanisms that govern this process remain problematic as commercially available tissue culture material can only sustain 2D monolayer or 3D aggregate/spheroid cultures. This necessitates the development of a system that can accommodate for cancer cell aggregation-disaggregation as a single dynamic process, without the disruption of passaging cells between alternate substrates. This study describes a procedure for modifying tissue culture polystyrene (TCP) to produce a fluoro-silica (FS) surface which preferentially promotes the deposition of a distinct profile of proteins/factors from serum which mediate the transient aggregation of human breast cancer cell lines. This modified surface therefore provides an experimental platform for better understanding cancer cell aggregation-disaggregation events in vitro, and their influence on the establishment of metastatic disease in patients with cancer.

show abstract

“…Среди этих молекул следует выделить такие, как нейтрофильная эластаза (NE), катепсин, аргиназа-1 (ARG1), матриксная металлопротеиназа-9 (MMP-9) и др. [57][58][59].…”

unclassified

Role of Cells of Innate Immunity in the Development of Malignant Tumors of the Brain

Lysіаniy¹,

Belskaya²,

Gnіdkova³

et al. 2019

Immun. and Allerg.: Sci. and Pract.

View full text Add to dashboard Cite

This review presents data on changes in the activity of cells of innate and acquired immunity, namely leukocytes, neutrophils, platelets and lymphocytes in various malignant human tumors, including brain tumors. It was shown that against the background of immunosuppression of specific immunity, especially antitumor reactions, which are caused by factors such as prostaglandin E2, TGF-β, indolamine-2,3-dioxigenase (IDO) and interleukin (IL) -10, which leads to a decrease the sensitivity of T cells to proinflammatory signals and the ineffectiveness of the presentation of tumor antigens to immune cells, activation and polarization of innate immunity cells, namely neutrophils, macrophages and platelets, occurs. Macrophages are important immune cells of the microenvironment in a tumor site that change their phenotype from M1 cells with antitumor activity to M2, which enhance tumor growth. The release of metalloprotheasis from platelet α -granules destroys the components of the extracellular matrix, increases the ability of cancer cells to pass through the endothelial barrier, penetrate the parenchyma and create metastatic tissue damage. Previously, neutrophils were mainly considered as cells of the body’s first line of defense, mainly with antimicrobial functions, but now they are regarded as cells with tumor-stimulating, “protumorogenic” activity, since in many types of cancer an increased level of neutron is determined with a reduced content of lymphocytes in the peripheral blood and this is associated with a poor prognosis of the disease. The review analyzes the hypothesis that there are three subpopulations of neutrophils in cancer: normal high density neutrophils, immature low density neutrophils (G-MDSC) and large mature low density neutrophils. These types of cells have different functions, for example, neutrophils with high density are antitumor, and with low density - cells that can stimulate tumor growth. ]. Neutrophils realize their activity through molecules such as neutrophilic elastase (NE), cathepsin, arginase 1 (ARG1), matrix metalloproteinase-9 (MMP-9). Multidirectional changes in the parts of the immune system depend on the histogenesis and degree of malignancy of the tumors and indicate differentiated use immunotropic drugs in cancer patients, some should suppress the activity of innate immunity cells, others stimulate the acquired immune response.

show abstract

Cathepsin G Induces Cell Aggregation of Human Breast Cancer MCF-7 Cells via a 2-Step Mechanism: Catalytic Site-Independent Binding to the Cell Surface and Enzymatic Activity-Dependent Induction of the Cell Aggregation

Cited by 31 publications

References 44 publications

Insulin‐like growth factor‐1 signaling is responsible for cathepsin G‐induced aggregation of breast cancer MCF‐7 cells

Insulin‐like growth factor‐1 signaling is responsible for cathepsin G‐induced aggregation of breast cancer MCF‐7 cells

Development of an hydrophobic fluoro-silica surface for studying homotypic cancer cell aggregation–disaggregation as a single dynamic process in vitro

Role of Cells of Innate Immunity in the Development of Malignant Tumors of the Brain

Contact Info

Product

Resources

About