Giant cell formation: the way to cell death or cell survival?

AbstractThe study of giant cells in populations of different tumor cells and evaluation of their role in cancer development is an expanding field. The formation of giant cells has been shown to be followed by mitotic catastrophe, apoptosis, necrosis, and other types of cell elimination. Reports also demonstrate that giant cells can escape cell death and give rise to new cancer cells. However, it is not known if the programmed cell death is involved in this type of cell cycle disorders. Here we describe principal events that are observed during giant cell formation. We also consider the role of giant cells in cancer development, taking into account both published work and our own recent data in this field.

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PATHOLOGY IN LEUKEMIA COMPLICATED BY FATAL MEASLES

PEDIATRICS ◽

10.1542/peds.21.3.436 ◽

1958 ◽

Vol 21 (3) ◽

pp. 436-442

Author(s):

C. Lenore Simpson ◽

Donald Pinkel

Keyword(s):

Lymph Nodes ◽

Giant Cell ◽

Inclusion Bodies ◽

Fatal Case ◽

Cell Formation ◽

Giant Cells ◽

Giant Cell Formation

A fatal case of measles complicating leukemia in an infant is reported. Giant-cell pneumonia and a few giant cells in lymph nodes were seen as in previously reported cases. In addition, necroses in liver, lymph nodes, thymus, pancreas and kidney associated with giant-cell formation and inclusion bodies were observed.

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Growth hormone induces mitotic catastrophe of podocytes and contributes to proteinuria

10.1101/597344 ◽

2019 ◽

Author(s):

Rajkishor Nishad ◽

Dhanunjay Mukhi ◽

Ashish Kumar Singh ◽

Kumaraswami Chintala ◽

Prasad Tammineni ◽

...

Keyword(s):

Cell Cycle ◽

Growth Hormone ◽

Cell Death ◽

Diabetic Nephropathy ◽

Notch Signaling ◽

Mitotic Catastrophe ◽

Podocyte Injury ◽

Tgf Β1 ◽

Notch Activation

AbstractPodocytes are integral members of the filtration barrier in the kidney and are crucial for glomerular permselectivity. Podocytes are highly differentiated and vulnerable to an array of noxious stimuli during various clinical conditions whereas podocyte loss plays a key role in progressive glomerular diseases. Elevated circulating growth hormone (GH) levels are associated with podocyte injury and proteinuria in diabetics. Previous studies have shown that podocytes express GH receptors (GHR), and induce Notch signaling when exposed to GH. However, the precise mechanism(s) by which excess GH elicits podocytopathy remains to be elucidated. In the present study, we demonstrate that GH induces cognate TGF-β1 signaling and provokes cell cycle re-entry of otherwise quiescent podocytes. Though, differentiated podocytes re-enter the cell cycle in response to GH and TGF-β1 unable to accomplish cytokinesis, despite nuclear division. Owing to this aberrant cell-cycle events significant amount of GH or TGF-β1 treated cells remain binucleated and undergo mitotic catastrophe. Importantly, inhibition of GHR, TGFBR1, or Notch signaling prevented cell cycle re-entry and protects podocyte from cell death. Furthermore, inhibition of Notch activation prevents GH-dependent podocyte injury and proteinuria. Kidney biopsy sections from patients with diabetic nephropathy show activation of Notch signaling and bi-nucleated podocytes. All these data confirm that excess GH induces Notch1 signaling via TGF-β1 and contributes to the mitotic catastrophe of podocytes. This study highlights the role of aberrant GH signaling in the podocytopathy and the potential application of inhibitors of TGF-β1 or Notch inhibitors as a therapeutic agent for diabetic nephropathy.Significance StatementElevated circulating levels of growth hormone (GH) associated with glomerular hypertrophy and proteinuria. Whereas decreased GH action protected against proteinuria. Podocytes are highly differentiated cells that play a vital role in glomerular filtration and curb protein loss. The direct role of GH in podocytes is the focus of our study. We found that GH induces TGF-β1 and both provoke cell cycle re-entry of podocytes in Notch1 dependent manner. Notch activation enables the podocytes to accomplish karyokinesis, but not cytokinesis owing to which podocytes remain binucleated. Binucleated podocytes that were observed during GH/TGF-β1 treatment are susceptible to cell death. Our study highlighted the fact that enforcing the differentiated podocytes to re-enter the cell cycle results in mitotic catastrophe and permanent loss.

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Sucrose-mediated giant cell formation in the genus Neisseria

Canadian Journal of Microbiology ◽

10.1139/m76-065 ◽

1976 ◽

Vol 22 (3) ◽

pp. 431-434 ◽

Cited By ~ 2

Author(s):

K. G. Johnson ◽

I. J. Mcdonald

Keyword(s):

Giant Cell ◽

Cell Formation ◽

Giant Cells ◽

Growth Conditions ◽

Normal Cells ◽

Giant Cell Formation ◽

Neisseria Sicca ◽

Neisseria Perflava

Growth of Neisseria perflava, Neisseria cinerea, and Neisseria sicca strain Kirkland in media supplemented with sucrose (0.5 to 5.0% w/v) resulted in the formation of giant cells. Response to sucrose was specific in that a variety of other carbohydrates did not mediate giant cell formation. Giant cells appeared only under growth conditions and did not lyse upon transfer to medium lacking sucrose or upon resuspension in hypotonic media. Reversion of giant to normal cells occurred when giant cells were used as inocula and allowed to multiply in media lacking sucrose.

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Delayed Cell Death, Giant Cell Formation and Chromosome Instability Induced by X-irradiation in Human Embryo Cells

Journal of Radiation Research ◽

10.1269/jrr.40.311 ◽

1999 ◽

Vol 40 (4) ◽

pp. 311-322 ◽

Cited By ~ 30

Author(s):

KANAKLATA ROY ◽

SEIJI KODAMA ◽

KEIJI SUZUKI ◽

MASAMI WATANABE

Keyword(s):

Cell Death ◽

Giant Cell ◽

Human Embryo ◽

Chromosome Instability ◽

Cell Formation ◽

Delayed Cell Death ◽

Giant Cell Formation ◽

Embryo Cells ◽

X Irradiation

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High-Temperature Sintering of Xenogeneic Bone Substitutes Leads to Increased Multinucleated Giant Cell Formation: In Vivo and Preliminary Clinical Results

Journal of Oral Implantology ◽

10.1563/aaid-joi-d-14-00168 ◽

2015 ◽

Vol 41 (5) ◽

pp. e212-e222 ◽

Cited By ~ 23

Author(s):

Mike Barbeck ◽

Samuel Udeabor ◽

Jonas Lorenz ◽

Markus Schlee ◽

Marzellus Grosse Holthaus ◽

...

Keyword(s):

High Temperature ◽

Inflammatory Response ◽

Giant Cell ◽

Multinucleated Giant Cell ◽

Cell Formation ◽

Giant Cells ◽

Clinical Aspects ◽

Multinucleated Giant Cells ◽

Giant Cell Formation ◽

Multinucleated Giant Cell Formation

The present preclinical and clinical study assessed the inflammatory response to a high-temperature–treated xenogeneic material (Bego-Oss) and the effects of this material on the occurrence of multinucleated giant cells, implantation bed vascularization, and regenerative potential. After evaluation of the material characteristics via scanning electron microscopy, subcutaneous implantation in CD-1 mice was used to assess the inflammatory response to the material for up to 60 days. The clinical aspects of this study involved the use of human bone specimens 6 months after sinus augmentation. Established histologic and histomorphometric analysis methods were applied. After implantation, the material was well integrated into both species without any adverse reactions. Material-induced multinucleated giant cells were observed in both species and were associated with enhanced vascularization. These results revealed the high heat treatment led to an increase in the inflammatory tissue response to the biomaterial, and a combined increase in multinucleated giant cell formation. Further clarification of the differentiation of the multinucleated giant cells toward so-called osteoclast-like cells or foreign-body giant cells is needed to relate these cells to the physicochemical composition of the material.

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Role of TRPV4 mechanosensing in foreign body response and giant cell formation

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.01995 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Shaik O. Rahaman ◽

Rakesh K. Arya ◽

Rishov Goswami

Keyword(s):

Foreign Body ◽

Giant Cell ◽

Cell Formation ◽

Foreign Body Response ◽

Giant Cell Formation ◽

Body Response

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Observations on Giant Cells in Potato Roots Infected with Heterodera rostochiensis

Journal of Helminthology ◽

10.1017/s0022149x00019544 ◽

1958 ◽

Vol 32 (3) ◽

pp. 135-144 ◽

Cited By ~ 8

Author(s):

C. S. Cole ◽

H. W. Howard

Keyword(s):

Giant Cell ◽

Secondary Xylem ◽

Cell Formation ◽

Giant Cells ◽

Vascular Strand ◽

Infested Soil ◽

Giant Cell Formation ◽

Parenchyma Cells ◽

Granular Cytoplasm ◽

Heterodera Rostochiensis

Giant cell formation was studied in the roots of potatoes grown in a soil infested with Heterodera rostochiensis.Some indication of giant cell formation was found in roots fixed 14 days after planting of sprouted tubers in the infested soil.Giant cells may be formed by the cells of the cortex, the endodermis, the pericycle and the parenchyma cells of the central vascular strand.The first giant cells appear to be formed in the cortex and pericycle.Giant cells in the cortex are only found near the head of an eelworm.Giant cell formation by the parenchyma cells of the central vascular strand leads to no cambium and hence no secondary xylem being produced in those sectors of the root where they occur.The occurrence of sectors of the root in which there is no secondary xylem gives the central vascular strand an irregular appearance.Some giant cells may be multinucleate. They all have granular cytoplasm.

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Infantile Liver Giant Cells: Immunohistological Study of Their Proliferative State and Possible Mechanisms of Formation

Pediatric and Developmental Pathology ◽

10.1007/s100249900134 ◽

1999 ◽

Vol 2 (4) ◽

pp. 353-359 ◽

Cited By ~ 30

Author(s):

George Koukoulis ◽

Giorgina Mieli-Vergani ◽

Bernard Portmann

Keyword(s):

Giant Cell ◽

Cell Formation ◽

Normal Liver ◽

Giant Cells ◽

Ki 67 ◽

Proliferation Markers ◽

Giant Cell Formation ◽

Mechanisms Of Formation ◽

Regenerative Cells ◽

Immunohistological Study

The mechanism of liver giant cell formation is not clarified. Some authors consider the giant cells regenerative, others, degenerative. Paraffin sections of 10 archival cases of idiopathic neonatal hepatitis (INH), 8 of extrahepatic biliary atresia (EHBA), and 5 normal liver samples were immunostained with two well-characterized cell proliferation markers: anti-PCNA monoclonal antibody (MAb) (clone PC-10) and MAb MIB-1, which detects Ki-67, a nuclear proliferation-related antigen. In addition, polyclonal antibody to carcinoembryonic antigen (CEA) was used to identify remnants of canalicular, therefore hepatocytic, membranes in giant cells. Quantitative analysis of immunostaining was done by estimating PCNA and Ki-67 indices separately in giant cells and in nongiant hepatocytes. In normal samples, mean PCNA and Ki-67 indices were 1.22% and 0.74%, respectively. In the cases of INH and EHBA, only a small minority of giant cells showed PCNA or Ki-67 staining limited to occasional peripherally located nuclei. PCNA and Ki-67 indices were significantly higher in the non–giant cell compartment. CEA staining was seen only in rare giant cells as centrally located canalicular remnants bordered by polarized nuclei, suggesting that they had been formed from rosettes through dissolution of cell membranes. Other giant cells shared CEA-labeled canalicular membranes with mononuclear hepatocytes in rosettes. These findings indicate that the giant cells in INH and EHBA are not regenerative cells, they are not formed by amitotic division of nuclei in syncytia, and that fusion of rosette-forming hepatocytes is a possible mechanism of their formation.

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