Pituitary folliculo-stellate-like cells stimulate somatotropic pituitary tumor growth in nude mice

Abstract

A new cell line (TtT/GF) established from a murine pituitary thyrotropic tumor having characteristics similar to those of pituitary folliculo-stellate cell (FS cell) was implanted into nude mice together with cells from a rat pituitary somatotrophic tumor cell line (MtT/S) to determine whether the former enhances pituitary tumor growth. For as long as 2-3 mo after implantation, MtT/S cells implanted either alone or together with fibroblasts formed either no tumors or only very small tumors in the nude mice. In contrast, all of the nude mice that had received MtT/S cells implanted together with TtT/GF cells developed large tumors. Furthermore, the mice bearing the MtT/S and TtT/GF implants showed a significantly higher body weight and serum growth hormone level than those bearing only MtT/S cells or a combination of MtT/S cells and fibroblasts. The TtT/GF cell line itself had no tumorigenicity during the experimental period. Therefore, the TtT/GF cell line as a model of FS cells enhanced pituitary endocrine cell tumor formation. Additionally, immunocytochemistry showed that TtT/GF cells positive for glial fibrillary acidic protein (GFAP) or S-100 protein were present in the parenchymatous tissue elements or connective tissue surrounding the tumor nests. In the parenchymatous tissue, the TtT/GF cells exhibited a stellate appearance and surrounded neighboring tumor cells with their long cell processes. These results suggest that TtT/GF cells can serve as a model for pituitary FS cells, and are capable of stimulating pituitary tumor growth either by modifying the microenvironment or producing growth factors.

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

“…Here we demonstrate the participation of gp130 in auto-paracrine stimulation of in vivo MtT/S cell growth using as model the dependence of the somatotrophic MtT/S cell line on the folliculostellate TtT/GF cell line to induce tumour formation in nude mice (23).…”

“…These data provide evidence supporting a link between gp130 and pituitary abnormal growth. Participation of gp130 cytokines in pituitary gland tumorigenesis is further underlined by evidence indicating that the MtT/S somatotrophic cell line depends on the IL-6-and LIF-producing TtT/GF FS cell line to generate tumours in nude mice (23). 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.…”

Pituitary adenylate cyclase-activating polypeptide, interleukin-6 and glucocorticoids regulate the release of vascular endothelial growth factor in pituitary folliculostellate cells

“…Very recently it has been shown that VEGF is up-regulated in response to estrogen in as yet unidentified pituitary cells of Fischer 344 rats, indicating an early onset of angiogenesis during the development of estrogen-induced prolactinomas in these animals (Banerjee et al 1997). Furthermore, it has been reported that TtT/GF cells are essential for pituitary tumor formation in nude mice, probably by supporting angiogenesis (Koyama et al 1995). However, VEGF-producing FS cells are normally absent or rare within adenomas (Marin et al 1992, Ueta et al 1995, but it has been reported that a transition zone exists between the adenoma and the normal pituitary tissue that is extremely rich in FS cells (Marin et al 1992, Farnoud et al 1994.…”

gp130 cytokine signaling in the pituitary gland: a paradigm for cytokine–neuro-endocrine pathways

“…IL-6 has been also reported to stimulate growth of rat tumor pituitary cells and of TtT/GF cells (27,28). Accordingly, the latter IL-6-producing cell line stimulates growth of somatotrophic tumor cells in nude mice (29). LIF released from primary bovine pituitary cultures can also suppress the proliferation of aortic endothelial cells and is therefore considered as a factor regulating pituitary angiogenesis (22).…”