Formation of autocrine loops in human cerebral meningioma tissue by leukemia inhibitor factor, interleukin-6, and oncostatin M: inhibition of meningioma cell growth in vitro by recombinant oncostatin M

It has been demonstrated that growth of cerebral meningiomas found in humans is controlled by a variety of factors, including growth factors, aminergic agents, neuropeptides, and steroids. The authors investigated the presence and function of the cytokines leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and oncostatin M (OSM) on meningioma cell proliferation. Active transcription of LIF, IL-6, OSM, their related receptors (LIF-R, IL-6-R, gp130), and the consecutive signal-transducing molecules (STAT 1, STAT 3, and STAT 5a) were analyzed in reverse transcriptase-polymerase chain reaction experiments. The presence of endogenous LIF, IL-6, and OSM proteins was demonstrated in the supernatant of cultured meningioma cells using enzyme-linked immunosorbent assay and Western blot experiments, thus indicating an autocrine signaling pathway for all three cytokines. The biological function of all three cytokines was evaluated by studying their effects on meningioma cell growth. Recombinant LIF and IL-6 showed no significant growth modulating effects; however, recombinant OSM decreased meningioma cell growth by 66%. The antiproliferative potency of OSM was demonstrated by cell count experiments, [3H]thymidine incorporation assay, and cell cycle analysis. These in vitro data support the concept that growth of meningioma cells may be modulated by cytokines and also indicates that recombinant OSM may be one of the future candidates for use in the adjuvant treatment of inoperable and recurrent meningiomas.

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Formation of autocrine loops in human cerebral meningioma tissue by leukemia inhibitor factor, interleukin-6, and oncostatin M: inhibition of meningioma cell growth in vitro by recombinant oncostatin M

Journal of Neurosurgery ◽

10.3171/jns.1998.88.3.0541 ◽

1998 ◽

Vol 88 (3) ◽

pp. 541-548 ◽

Cited By ~ 25

Author(s):

Uwe M. H. Schrell ◽

Hans Uwe Koch ◽

Rolf Marschalek ◽

Thomas Schrauzer ◽

Marc Anders ◽

...

Keyword(s):

Cell Growth ◽

Interleukin 6 ◽

Oncostatin M ◽

Enzyme Linked Immunosorbent Assay ◽

Autocrine Signaling ◽

Content Type ◽

Meningioma Cell ◽

Leukemia Inhibitor Factor ◽

Fine Print

Object. It has been demonstrated that growth of cerebral meningiomas found in humans is controlled by a variety of factors, including growth factors, aminergic agents, neuropeptides, and steroids. To further our knowledge of this process, the authors investigated the presence and function of the cytokines leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and oncostatin M (OSM) on meningioma cell proliferation. Methods. Active transcription of LIF, IL-6, and OSM, their related receptors (LIF-R, IL-6-R, and gp130), and the consecutive signal-transducing molecules (STAT 1, STAT 3, and STAT 5a) were analyzed in reverse transcriptase—polymerase chain reaction experiments. The presence of endogenous LIF, IL-6, and OSM proteins was demonstrated in the supernatant of cultured meningioma cells using the enzyme-linked immunosorbent assay and Western blot experiments, thus indicating an autocrine signaling pathway for all three cytokines. The biological function of all three cytokines was evaluated by studying their effects on meningioma cell growth. Recombinant LIF and IL-6 showed no significant growth modulating effects; however, recombinant OSM decreased meningioma cell growth by 66%. The antiproliferative potency of OSM was demonstrated by cell count experiments, the [3H]thymidine incorporation assay, and cell cycle analysis. Conclusions. These in vitro data support the concept that growth of meningioma cells may be modulated by cytokines, and they also indicate that recombinant OSM may be one future candidate for use in the adjuvant treatment of inoperable and recurrent meningiomas.

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Myeloma cell growth arrest, apoptosis, and interleukin-6 receptor modulation induced by EB1089, a vitamin D3 derivative, alone or in association with dexamethasone

Blood ◽

10.1182/blood.v88.12.4659.bloodjournal88124659 ◽

1996 ◽

Vol 88 (12) ◽

pp. 4659-4666 ◽

Cited By ~ 30

Author(s):

D Puthier ◽

R Bataille ◽

S Barille ◽

MP Mellerin ◽

JL Harousseau ◽

...

Keyword(s):

Multiple Myeloma ◽

Cell Growth ◽

Vitamin D3 ◽

Interleukin 6 ◽

Plasma Cells ◽

Growth Arrest ◽

Myeloma Cell ◽

Oncostatin M ◽

Receptor Modulation

We have previously shown that malignant plasma cells expressed the specific receptor for 1,25-dihydroxyvitamin D3 and that this derivative could significantly inhibit the proliferation of such malignant cells. More recently, new vitamin D3 derivatives have been generated with extraordinarily potent inhibitory effects on leukemic cell growth in vitro. These new data prompted us to (re)investigate the capacity of such new vitamin D3 derivatives to inhibit myeloma cell growth in comparison with that of dexamethasone, a potent antitumoral agent in multiple myeloma. In the current study, we show that EB1089, a new vitamin D3 derivative, (1) induces G1 growth arrest of human myeloma cells, which is only partially reversed by interleukin-6 (IL-6); (2) induces apoptosis in synergy with dexamethasone, IL-6, leukemia-inhibitory factor, and Oncostatin M, with an agonistic anti-gp130 monoclonal antibody being unable to prevent this apoptosis; (3) downregulates both the gp80 (ie, the alpha chain of the IL-6 receptor [IL-6Ralpha]) expression on malignant plasma cells and the production of soluble IL-6Ralpha, and finally (4) inhibits the deleterious upregulation of gp80 expression induced by dexamethasone while limiting the dexamethasone-induced upregulation of gp130 expression. Considering that these in vitro effects of EB1089 have been observed at doses obtainable in vivo (without hypercalcemic effects), our present data strongly suggest that EB1089 could have a true interest in the treatment of multiple myeloma, especially in association with dexamethasone.

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Survival and Function of Fibroblasts Stored as Stock Cultures at a Non-freezing Temperature

Alternatives to Laboratory Animals ◽

10.1177/026119299302100215 ◽

1993 ◽

Vol 21 (2) ◽

pp. 206-209

Author(s):

Anders H. G. Andrén ◽

Anders P. Wieslander

Keyword(s):

Cell Growth ◽

Cell Line ◽

Cell Lines ◽

Fibroblast Cell ◽

Freezing Temperature ◽

Mouse Fibroblast ◽

Toxic Response ◽

Normal Manner ◽

And Function

Cytotoxicity, measured as inhibition of cell growth of cultured cell lines, is a widely used method for testing the safety of biomaterials and chemicals. One major technical disadvantage with this method is the continuous routine maintenance of the cell lines. We decided to investigate the possibility of storing stock cultures of fibroblasts (L-929) in an ordinary refrigerator as a means of reducing the routine workload. Stock cultures of the mouse fibroblast cell line L-929 were prepared in plastic vials with Eagle's minimum essential medium. The vials were stored in a refrigerator at 4–10°C for periods of 7–31 days. The condition of the cells after storage was determined as cell viability, cell growth and the toxic response to acrylamide, measured as cell growth inhibition. We found that the L-929 cell line can be stored for 2–3, weeks with a viabilty > 90% and a cell growth of about 95%, compared to L-929 cells grown and subcultured in the normal manner. The results also show that the toxic response to acrylamide, using refrigerator stored L-929 cells, corresponds to that of control L-929 cells. We concluded that it is possible to store L-929 cells in a refrigerator for periods of up to 3 weeks and still use the cells for in vitro cytotoxic assays.

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Schisandrin B Attenuates Colitis-Associated Colorectal Cancer through SIRT1 Linked SMURF2 Signaling

The American Journal of Chinese Medicine ◽

10.1142/s0192415x21500841 ◽

2021 ◽

pp. 1-17

Author(s):

Zhichen Pu ◽

Weiwei Zhang ◽

Minhui Wang ◽

Maodi Xu ◽

Haitang Xie ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cell Growth ◽

Protein Expression ◽

Hct116 Cell ◽

Enzyme Linked Immunosorbent Assay ◽

Schisandrin B ◽

In Vivo Models

Colon cancer, a common type of malignant tumor, seriously endangers human health. However, due to the relatively slow progress in diagnosis and treatment, the clinical therapeutic technology of colon cancer has not been substantially improved in the past three decades. The present study was designed to investigate the effects and involved mechanisms of schisandrin B in cell growth and metastasis of colon cancer. C57BL/6 mice received AOM and dextran sulfate sodium. Mice in treatment groups were gavaged with 3.75–30 mg/kg/day of schisandrin B. Transwell chamber migration, enzyme-linked immunosorbent assay (ELISA), Western blot analysis, immunoprecipitation (IP) and immunofluorescence were conducted, and HCT116 cell line was employed in this study. Data showed that schisandrin B inhibited tumor number and tumor size in the AOD+DSS-induced colon cancer mouse model. Schisandrin B also inhibited cell proliferation and metastasis of colon cancer cells. We observed that schisandrin B induced SMURF2 protein expression and affected SIRT1 in vitro and in vivo. SMURF2 interacted with SIRT1 protein, and there was a negative correlation between SIRT1 and SMURF2 expressions in human colorectal cancer. The regulation of SMURF2 was involved in the anticancer effects of schisandrin B in both in vitro and in vivo models. In conclusion, the present study revealed that schisandrin B suppressed SIRT1 protein expression, and SIRT1 is negatively correlated with the induction of SMURF2, which inhibited cell growth and metastasis of colon cancer. Schisandrin B could be a leading compound, which will contribute to finding novel potential agents and therapeutic targets for colon cancer.

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Interleukin-6 is a potent myeloma-cell growth factor in patients with aggressive multiple myeloma

Blood ◽

10.1182/blood.v74.1.11.11 ◽

1989 ◽

Vol 74 (1) ◽

pp. 11-13 ◽

Cited By ~ 182

Author(s):

XG Zhang ◽

B Klein ◽

R Bataille

Keyword(s):

Multiple Myeloma ◽

Growth Factor ◽

Cell Growth ◽

Interleukin 6 ◽

Myeloma Cell ◽

S Phase ◽

Myeloma Cells ◽

Severity Of The Disease

Abstract It has recently been demonstrated that interleukin-6 (IL-6) is a potent myeloma-cell growth factor in the majority of patients with multiple myeloma (MM). Using an anti-bromodeoxyuridine monoclonal antibody (MoAb) to specifically count myeloma cells in the S-phase (ie, labeling index, LI), we demonstrate that the IL-6 responsiveness of myeloma cells in vitro is directly correlated with their LI in vivo. Myeloma cells from all 13 patients with high LIs in vivo (greater than or equal to 1%) responded in vitro to IL-6, the strongest response occurring in cells from five patients with plasma-cell leukemia. In contrast, the cells of only two of eight patients with low myeloma-cell LIs in vivo (less than 1%) responded to IL-6 in vitro. After seven days of culturing with 1,000 U/mL recombinant IL-6 (rIL-6), the median LI value in the first group of patients (in vivo LI greater than or equal to 1%) was 11%, ie 11 times higher (P less than .01) than the median LI value (1%) in the second group of patients (in vivo LI less than 1%). Thus, the in vitro IL-6 responsiveness of myeloma cells is directly related to their in vivo proliferative status, and hence to the severity of the disease.

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REGULATION OF MENINGIOMA CELL GROWTH IN VITRO BY POLYAMINES

Journal of Neuropathology & Experimental Neurology ◽

10.1097/00005072-197110000-00012 ◽

1971 ◽

Vol 30 (4) ◽

pp. 698-713 ◽

Cited By ~ 10

Author(s):

P. E. DUFFY ◽

R. DEFENDINI ◽

L. T. KREMZNER

Keyword(s):

Cell Growth ◽

Meningioma Cell

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Suppressive effects of dehydroepiandrosterone and the nuclear factor-κB inhibitor parthenolide on corticotroph tumor cell growth and function in vitro and in vivo

Journal of Endocrinology ◽

10.1677/joe.1.06418 ◽

2006 ◽

Vol 188 (2) ◽

pp. 321-331 ◽

Cited By ~ 15

Author(s):

T Taguchi ◽

T Takao ◽

Y Iwasaki ◽

M Nishiyama ◽

K Asaba ◽

...

Keyword(s):

Cell Growth ◽

Tumor Growth ◽

Tumor Cells ◽

Survivin Expression ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Aging Effects ◽

And Function

Dehydroepiandrosterone (DHEA) is believed to have an anti-tumor effect, as well as anti-inflammatory, antioxidant, and anti-aging effects. To clarify the possible inhibitory action of DHEA on pituitary tumor cells, we tested the effects of DHEA, alone or in combination with the nuclear factor-κB (NF-κB) inhibitor parthenolide (PRT), on AtT20 corticotroph cell growth and function both in vitro and in vivo. We found that, in vitro, DHEA and PRT had potent inhibitory effects on pro-opiomelanocortin and NF-κB-dependent gene expression. They also suppressed the transcription activity of survivin, a representative anti-apoptotic factor, and induced apoptosis in this cell line. Furthermore, using BALB/C nude mice with xenografts of AtT20 cells in vivo, we found that the combined administration of DHEA and PRT significantly attenuated tumor growth and survivin expression. The treatment also decreased the elevated plasma corticosterone levels and ameliorated the malnutrition induced by tumor growth. Altogether, these results suggested that combined treatments of DHEA and PRT potently inhibit the growth and function of corticotroph tumor cells both in vitro and in vivo. This effect may, at least partly, be caused by the suppressive effects of these compounds, such as survivin and other inhibitor of apoptosis proteins, on NF-κB-mediated gene transcription.

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