Characterization of Murine Pituitary-Derived Cell Lines Tpit/F1, Tpit/E and TtT/GF

Yoshida, Saishu; Higuchi, Masashi; Ueharu, Hiroki; Nishimura, Naoto; Tsuda, Mitsuyoshi; Yako, Hideji; Chen, Mo; Mitsuishi, Hideo; Sano, Yoshiya; Katō, Takako; Kato, Yukio

doi:10.1262/jrd.2014-031

Cited by 9 publications

(1 citation statement)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several years ago, it was suggested that spindle cell oncocytomas represent the long-anticipated tumor of folliculostellate cytogenesis (Roncaroli et al 2002); however, these have now been shown to be derived from pituicytes of the posterior lobe (Mete et al 2013). The strong expression of NG2 in folliculostellate cells of the adenohypophysis noted in our study is consistent with the recent description of NG2 expression in the clonal TtT cell line that is thought to be derived from folliculostellate cells (Yoshida et al 2014). Nevertheless, it was quite unexpected that we found no evidence of proliferation or transformation of those cells in the mouse model.…”

Section: Discussionsupporting

confidence: 92%

NG2 targets tumorigenic Rb inactivation in Pit1-lineage pituitary cells

Tateno

Nakano-Tateno

Ezzat

et al. 2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

The proteoglycan neuron-glial antigen 2 (NG2) is expressed by oligodendrocyte progenitors, pericytes, and some cancerous cells where it is implicated in tumor development. We examined mice with NG2-driven pRb inactivation. Unexpectedly, NG2-Cre:pRb flox/flox mice developed pituitary tumors with high penetrance. Adenohypophysial neoplasms developed initially as multifocal lesions; by 1 year, large tumors showed brain invasion. Immunohistochemistry identified these as Pit1-lineage neoplasms, with variable immunoreactivity for growth hormone, prolactin, thyrotropin, and α-subunit of glycoprotein hormones. Other than modest hyperprolactinemia, circulating hormone levels were not elevated. To determine the role of NG2 in the pituitary, we investigated NG2 expression. Immunoreactivity was identified in anterior and posterior lobes but not in the intermediate lobe of the mouse pituitary; in the adenohypophysis, folliculostellate cells had the strongest NG2 immunoreactivity but showed no proliferation in response to Rb inactivation. Pit1-positive adenohypophysial cells were positive for NG2, but corticotroph and gonadotroph cells were negative. RT-PCR revealed NG2 expression in normal human pituitary and human pituitary tumors; immunohistochemistry localized NG2 in nontumorous human adenohypophysis with strongest positivity in folliculostellate cells, and in tumors of all types except corticotrophs. Functional studies in GH4 mammosomatotrophs showed that NG2 increases prolactin (PRL), reduces growth hormone (GH) expression, and enhances cell adhesion without influencing proliferation. In conclusion, NG2-driven pRb inactivation results in pituitary tumors that mimic endocrinologically inactive Pit1-lineage human pituitary tumors. This model identifies a role for NG2 in pituitary cell-type-specific functions and unmasks a protective role from Rb inactivation in folliculostellate cells; it can be used for further research, including preclinical testing of novel therapies.

show abstract

Section: Discussionsupporting

confidence: 92%

NG2 targets tumorigenic Rb inactivation in Pit1-lineage pituitary cells

Tateno

Nakano-Tateno

Ezzat

et al. 2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

PRRX1- and PRRX2-positive mesenchymal stem/progenitor cells are involved in vasculogenesis during rat embryonic pituitary development

et al. 2015

View full text Add to dashboard Cite

We have recently shown that cells positive for the paired-related homeobox transcription factors PRRX1 and PRRX2 occur in the rat pituitary, and that they are derived from two different origins: pituitary-derived cells positive for stem cell marker SOX2 and extra-pituitary-derived cells negative for SOX2. In this study, we have further characterized the PRRX1- and PRRX2-positive cells that originate from extra-pituitary cells. Immunohistochemical analyses were performed with specific antibodies against PRRX1 and PRRX2 in order to clarify their roles in pituitary vasculogenesis. PRRX1- and PRRX2-positive cells were found in Atwell's recess and at the periphery of the pituitary on embryonic day 15.5 (E15.5). Several PRRX1-positive cells then invaded the anterior lobe, together with a few PRRX2-positive cells, on E16.5. Some PRRX1-positive cells were also positive for mesenchymal stem cell marker NESTIN. Moreover, some PRRX1/NESTIN double-positive cells showed characteristics of vascular endothelial cells with an Isolectin-B4-binding capacity. PRRX1 co-localized with vascular smooth muscle cell/pericyte marker α-smooth muscle actin in the deep area of Atwell's recess. We confirmed the presence of PRRX2/NESTIN double-positive cells at an entry area in Atwell's recess and at the periphery of the pituitary, but PRRX2 did not co-localize with Isolectin B4 or α-smooth muscle actin. These data suggest that PRRX1- and PRRX2-positive mesenchymal stem/progenitor cells are present at the periphery of the embryonic pituitary and at the entry from Atwell's recess and participate in pituitary vasculogenesis by differentiation into vascular endothelial cells and pericytes, whereas the presence of PRRX2 indicates much higher stemness than PRRX1.

show abstract

Clump formation in mouse pituitary-derived non-endocrine cell line Tpit/F1 promotes differentiation into growth-hormone-producing cells

et al. 2017

View full text Add to dashboard Cite

The adenohypophysis comprises six types of endocrine cells, including PIT1-lineage cells such as growth hormone (GH)-producing cells and heterogeneous non-endocrine cells, such as pituitary stem/progenitor cells as a source of endocrine cells. We determine the expression of characteristic stem cell marker genes, including sex-determining region Y-box 2 (Sox2), in mouse pituitary-derived non-endocrine cell lines Tpit/E, Tpit/F1 and TtT/GF. We observed high expression of fibroblast growth factor (FGF) receptors in Tpit/F1 cells, which we characterised by cultivation in medium containing a basic FGF and B27 supplement as used for neural stem-cell differentiation. A 4-day cultivation of Tpit/F1 produced floating embryonic stem-cell-like clumps accompanied by a three-fold increase in Sox2 expression. Passages in these clumps maintained the proliferative activity and Sox2 expression levels. After 10 days of cultivation, Tpit/F1 cell clumps were immuno-positive for SOX2 and Ki67 (proliferation marker) and loosely attached to the well bottom. An additional 10 days of cultivation induced the emergence of GH-positive/pituitary-specific transcription factor (PIT1)-negative cells showing migration from the clumps. Pit1 overexpression in attached cells could not induce GH production. Finally, we confirmed the presence of PIT1-negative GH-producing cells (3.2-7.7 % of all GH-positive cells) in rat pituitary. Thus, we demonstrate that Tpit/F1 has the plasticity to differentiate into one type of hormone-producing cell.

show abstract

Characterization of Murine Pituitary-Derived Cell Lines Tpit/F1, Tpit/E and TtT/GF

Cited by 9 publications

References 44 publications

NG2 targets tumorigenic Rb inactivation in Pit1-lineage pituitary cells

NG2 targets tumorigenic Rb inactivation in Pit1-lineage pituitary cells

PRRX1- and PRRX2-positive mesenchymal stem/progenitor cells are involved in vasculogenesis during rat embryonic pituitary development

Clump formation in mouse pituitary-derived non-endocrine cell line Tpit/F1 promotes differentiation into growth-hormone-producing cells

Contact Info

Product

Resources

About