Regulation of cell proliferation inhibitory and stimulatory factors diffused by 3T3 cultured cells

Harel, L; Blat, C.; Chatelain, Gilles

doi:10.1002/jcp.1041230120

Cited by 31 publications

(6 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is interesting to note that a high cell density and a low proliferation rate of the N2A cells were needed to obtain maximal secretion of the activity. This observation could suggest that this astroglia proliferation inhibitory activity might be related to an autocrine factor that is released by N2A cells exclusively at high cell densities and is able to inhibit the proliferation of N2A cells themselves (Holley et al, 1980;Hare1 et al, 1985;Steck et al, 1979;Wang and Hsu, 1986). However, because the activity found in N2A CM does not modify the proliferative status of N2A cells even when these cells are bioassayed at low density, a more likely explanation is that neuronal cells release one (or several) factors that specifically inhibit astroglial cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Cultured neurons release an inhibitor of astroglia proliferation (astrostatine)

Rogister

Leprince²,

Bonhomme

et al. 1990

J of Neuroscience Research

View full text Add to dashboard Cite

Using in vitro techniques, we looked for a possible downregulation of rat astroglia proliferation by neuronal cells. We demonstrate that medium conditioned by 7-day-old rat cerebellar granule neurons or by 16-day-old rat embryo hippocampal neurons strongly inhibits the proliferation of cultured astroglial cells. Two neuronal cell lines, the PC12 rat pheocromocytoma and the neuro 2A (N2A) murine neuroblastoma also release such an activity. This release in N2A-conditioned medium (CM) occurs when the cells are at high density and show a low proliferation rate. This activity is present in media conditioned by neuronal cells, but not in media conditioned by normal astrocytes, by two glioma cell lines, or by one fibroblastic cell line. This proliferation inhibitor addresses normal astrocytes: the proliferation of two glioma cell lines, of a fibroblastic cell line, and of the two neuronal cell lines (PC12, N2A) is not inhibited by N2A CM. Moreover, this activity is directed against type 1 astrocytes, but not against type 2. Using three different assays, we demonstrate that DNA synthesis by astroglial cells is inhibited. N2A CM has no cytotoxic effect on astrocytes and does not modify their overall protein synthesis. Using affinity and gel filtration chromatography, we show that this activity is associated with a protein whose molecular weight ranges between 15 and 20 kDa. The possible relationship between this N2A cell-derived astroglia proliferation inhibitor and other types of potential glial proliferation inhibitors has been investigated. A brain glycoprotein immunologically related to epidermal growth factor receptor (EGFR) was reported to inhibit astroglial cell proliferation in vitro. Using polyclonal and monoclonal antibodies against EGFR, we were unable to immunoprecipitate the astrocyte proliferation inhibitor in N2A CM or to demonstrate by immunoblotting the presence of an EGFR-like immunoreactivity in the N2A CM or in the active chromatographic fractions of N2A CM. Transforming growth factor beta (TGF beta) is a well-known modulator of the proliferation of various cell types and was shown to be present in N2A CM. Using a polyclonal anti-TGF beta antibody that recognizes TGF beta on Western blots of N2A CM, we were unable to immunoprecipitate the astrocyte proliferation inhibitor of N2A CM. It seems thus far that the neuronal astroglia proliferation inhibitor is a new protein for which we propose the name astrostatine.

show abstract

Section: Discussionmentioning

confidence: 99%

Cultured neurons release an inhibitor of astroglia proliferation (astrostatine)

Rogister

Leprince²,

Bonhomme

et al. 1990

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…The growth of cells in tissue culture systems involves the complex interaction between growth factors and growth inhibitory molecules (Lieberman, 1984;Harel et al, 1985). Growth factors have been shown to exert their biological effects through a n interaction with specific cell surface receptors.…”

mentioning

confidence: 99%

“…Although several soluble growth inhibitors (Wells and Mallucci, 1983;Harel et al, 1985) or membrane-bound inhibitors (Lieberman, 1984;Yaoi, 1984) have been isolated, purification of these growth inhibitory molecules to homogeneity has not been demonstrated. We have been interested in understanding the mechanisms of density-dependent regulation of cell growth for several years (Kinders et al, 1980;Kinders and Johnson, 1982;Johnson et al, 1985).…”

mentioning

confidence: 99%

Receptor occupancy by a bovine sialoglycopeptide inhibitor correlates with inhibition of protein synthesis

Bascom

Sharifi

Johnson

1986

Journal Cellular Physiology

View full text Add to dashboard Cite

We have isolated from bovine cerebral cortex cells and purified to homogeneity an 18,000 dalton, pl 3.0 sialoglycopeptide that inhibits protein synthesis and DNA synthesis of nontransformed but not transformed cells without affecting uptake of radiolabeled precursors. In this paper, we examine the relationship between the binding of the sialoglycopeptide inhibitor to 3T3 cells and inhibition of protein synthesis. Binding of the sialoglycopeptide to 3T3 cells was rapid at 37 degrees C and reached a maximum at 30 min; the binding at 37 degrees C was shown to be saturable and specific. Scatchard analysis of the binding indicated that 3T3 cells contained about 2 X 10(4) receptors/cell with a dissociation constant of 1.0-1.5 nM. Several lines of evidence indicated that receptor occupancy on 3T3 cells correlated with the protein synthesis inhibitory activity of the sialoglycopeptide. A comparison of the kinetics of inhibitor binding with the kinetics of protein synthesis inhibition demonstrated that binding directly correlated with the inhibition of protein synthesis, concentration-dependent inhibition of protein synthesis directly correlated with concentration-dependent receptor occupancy, and a direct correlation was also observed between the kinetics of inhibitor dissociation from its specific cell surface receptor and the kinetics of recovery from protein synthesis inhibition.

show abstract

“…act. 40-60 ~tCi/mmole) was added, at 1 ~tCi/1 x 10 6 cells, following the technique described by Harel et al [19]. The cells were incubated for 18 h and washed three times in the same medium.…”

Section: Treatment Of Animalsmentioning

confidence: 99%

Antimetastatic effect of immunomodulators from Nocardia opaca in mice and rats activation of peritoneal macrophages by these fractions

Barot‐Ciorbaru

Cornil²,

Grand-Perret

et al. 1987

Cancer Immunol Immunother

View full text Add to dashboard Cite

Nocardia delipidated cell mitogen (NDCM), a particulate fraction prepared from Nocardia opaca, injected i.p. in an oil/water emulsion to F6 rhabdomyosarcoma-bearing rats, inhibited the development of pulmonary metastases; 6 out of 10 rats were protected. Repeated i.p. administration of emulsified NDCM and of two other compounds, a Nocardia water soluble mitogen (NWSM a hydrosoluble fraction) and purified cell walls (CW, an insoluble macromolecular fraction) in Lewis lung carcinoma (LLC)-bearing mice resulted in a significant reduction of lung metastases. The efficiency of these fractions was enhanced by association with monokines. A combination regimen of NDCM, NWSM, and CW (100 micrograms/0.1 ml) and monokines (0.1 ml), injected i.p. in LLC-bearing mice, yielded a greater antimetastatic effect than either therapy alone. Peritoneal macrophages from mice which had been injected i.p. with NWSM or CW, when triggered either by TPA (tetradecanoyl phorbol acetate) or by zymosan, released large quantities of hydrogen peroxide and had a high rate of glucose consumption. These macrophages were activated as judged by their cytostatic activity against syngeneic P815 mastocytoma growth; they expressed biochemical markers which have been reported to characterize the activated state. Incubation of thioglycollate-elicited peritoneal macrophages with NWSM, and monokines for 72 h resulted in a cytotoxic activity against labeled LLC cells; addition of macrophage activating factor significantly increased the cytotoxic capacity of these macrophages. In view of this we postulate that the antimetastatic effect of soluble and insoluble N. opaca fractions and monokines might be mediated by activated peritoneal macrophages.

show abstract

Regulation of cell proliferation inhibitory and stimulatory factors diffused by 3T3 cultured cells

Cited by 31 publications

References 21 publications

Cultured neurons release an inhibitor of astroglia proliferation (astrostatine)

Cultured neurons release an inhibitor of astroglia proliferation (astrostatine)

Receptor occupancy by a bovine sialoglycopeptide inhibitor correlates with inhibition of protein synthesis

Antimetastatic effect of immunomodulators from Nocardia opaca in mice and rats activation of peritoneal macrophages by these fractions

Contact Info

Product

Resources

About