Interleukin-6 stimulates cell proliferation of rat pituitary clonal cell lines in vitro

Sawada, Takuya; Koike, Koji; Kanda, Yuki; Ikegami, Hiromasa; Jikihara, Hiroaki; Maeda, Takashi; Osako, Y.; Hirota, Kenji; Miyake, Akira

doi:10.1007/bf03349706

Cited by 45 publications

(24 citation statements)

References 44 publications

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“…We observed that the IL-6-stimulated increase in STAT3 activity levels was not very strong in control clones but was consistent and higher than in AS clones. It has also been reported that MtT/S cells respond to gp130 stimuli in proliferation studies (24). Our results show that gp130-AS clones have reduced proliferative capacity in response to gp130 stimuli compared with MtT/S wild-type cells or control (empty vector) and gp130-S clones.…”

Section: Discussionsupporting

confidence: 77%

“…Although the mechanism by which TtT/GF cells contribute to MtT/S cell tumorigenicity is not clear, one possible way might be through the liberation of cytokines and growth factors that stimulate MtT/S growth. In concordance with this hypothesis, it has been reported that MtT/S growth is enhanced in vitro by exogenous gp130 cytokines such as IL-6 (24).…”

Section: Introductionsupporting

confidence: 55%

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Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model

Graciarena

Carbia-Nagashima²,

Onofri

et al. 2004

European Journal of Endocrinology

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Objective: gp130 cytokines are placed as auto-paracrine regulators of pituitary function, since they, as well as their receptors, have been shown to be expressed in and to act in normal and tumoral anterior pituitary cells. The objective of this work was to study their involvement in a model that shows the interaction between different cellular types that participate in a tumorigenic process. Design: The dependence of a pituitary somatotrophic cell line (MtT/S) on a gp130 cytokine-producing folliculostellate (FS) cell line (TtT/GF) for tumorigenesis in vivo has been described. In order to study the participation of gp130 cytokines in the auto-paracrine stimulation of MtT/S growth, we generated MtT/S gp130 sense (gp130-S) and gp130 antisense (gp130-AS) clones stably transfected with pcDNA3/gp130 sense and pcDNA3/gp130 antisense vectors respectively. Methods and results: Functional characterization studies revealed that gp130-AS clones have an inhibited gp130 signalling, and proliferation studies showed that they have an impaired response to gp130 cytokines but respond normally to other independent stimuli. When injected into nude mice, MtT/S clones respond differently depending on cell number; at high concentrations MtT/S clones alone generated tumours equivalent in size to tumours derived from MtT/S plus TtT/GF cells. At low concentrations, MtT/S sense and control clones generated tumours of smaller size than tumours derived from these same clones plus TtT/GF cells, showing a dependence on FS cells. In both cases MtT/S gp130-AS clones had impaired tumour development. Furthermore, vessel density was significantly lower in tumours derived from gp130-AS plus TtT/GF cells. Conclusions: This study underlines the importance of gp130 cytokines in proliferation and establishes its role in auto-paracrine pituitary growth regulation.European Journal of Endocrinology 151 595-604

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Section: Discussionsupporting

confidence: 77%

Section: Introductionsupporting

confidence: 55%

Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model

Graciarena

Carbia-Nagashima²,

Onofri

et al. 2004

European Journal of Endocrinology

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“…The signal transducer gp130 mediates the effects of a number of different cytokines, such as IL-6, which inhibits the growth of normal pituitary cells and stimulates the growth of tumour cells (2,3) and is therefore supposedly a cytokine, which promotes adenoma expansion. IL-6 may support adenoma development and pathophysiology by autocrine/paracrine mechanisms since it has been reported to be synthesised and released by about 53 to 72% of pituitary adenomas (19,29).…”

Section: Discussionmentioning

confidence: 99%

Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas

et al. 2003

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Objective: Interleukin-6 (IL-6), a member of the gp130 cytokine family, is considered to be an important modulator of function and growth in endocrine anterior pituitary cells. In pituitary adenomas, where IL-6 is often produced by the tumour cells, it is thought to be involved in pituitary adenoma pathophysiology via autocrine/paracrine mechanisms. Methods: We have studied in primary cell cultures of human somatotroph adenomas whether IL-6 stimulates growth hormone secretion and whether intratumoral IL-6 is affected by various IL-6-regulating factors.Results: Interleukin-6 stimulated GH secretion in 10 out of 11 somatotroph adenoma cultures (1.4-to 6.5-fold above basal levels). In comparative studies the GH-stimulatory potency of IL-6 was identical, or even stronger, than that of GHRH. In eight out of 11 adenoma cell cultures, IL-6 production was observed. This suggests that GH production might be stimulated by IL-6 in an autocrine/paracrine manner in these tumours. Dexamethasone strongly inhibited basal IL-6 secretion in all IL-6-producing adenoma cell cultures, whereas the IL-6 inhibitory or stimulatory action of other factors (octreotide, transforming growth factor-b1, insulin-like growth factor-I, pituitary adenylate cyclase-activating peptide and oestradiol) were heterogeneous in the different adenomas. Only transforming growth factor-a consistently stimulated IL-6 secretion in all of the adenomas studied. Conclusions: Intratumoral IL-6, which is differently regulated by various factors, might contribute to excessive GH production in the majority of somatotroph adenomas.

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“…MtT/E cells do not produce any pituitary hormones and their growth is not stimulated by estrogen (Inoue et al 1990). The effect of interleukin-6 (IL-6) on cell growth is also different from the other endocrine cell lines (Sawada et al 1995). Interestingly, MtT/E cells are positive for Pit-1, which strongly suggests that MtT/E cells are committed to an endocrine cell lineage.…”

Section: Introductionmentioning

confidence: 99%

Multistep differentiation of GH-producing cells from their immature cells

Mogi

Goda

Mogi

et al. 2005

Journal of Endocrinology

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In order to study GH cell differentiation, we used the clonal cell lines called MtT/E and MtT/S cells, which were derived from a rat mammotrophic pituitary tumor. Although MtT/E cells are non-hormone-producing ones, Pit-1 protein is present in their nuclei, which suggests that MtT/E cells are progenitor cells of the Pit-1 cell lineage and have the potential to differentiate into hormoneproducing cells. On the other hand, MtT/S cells produce GH; however, the responsiveness to GH-releasing hormone (GHRH) is weak and only a small number of secretory granules are present in their cytoplasm, which suggests that MtT/S cells are premature GH cells. In order to differentiate into GH cells from MtT/E cells as a progenitor cell, we examined several differentiation factors and found that retinoic acid (RA) induced the differentiation of MtT/E cells into GH-producing cells. RAinduced GH cells partially matured with the glucocorticoid treatment; however, the responsiveness to GHRH on GH secretion was incomplete. In order to elucidate the mechanism underlying full differentiation of GH cells, we used MtT/S cells. We treated MtT/S cells with glucocorticoid and found that they differentiated into mature GH cells with many secretory granules in their cytoplasm and they responded well to GHRH. These results suggested that MtT/E and MtT/S cells are progenitor or premature GH cells, and show different responses to differentiation factors. Our data also suggested that GH cells differentiate from their progenitor cells through multistep processes.

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Interleukin-6 stimulates cell proliferation of rat pituitary clonal cell lines in vitro

Cited by 45 publications

References 44 publications

Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model

Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model

Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas

Multistep differentiation of GH-producing cells from their immature cells

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