Identification of CD133+ Cells in Pituitary Adenomas

Abstract

Stem-like cells in tumors are capable of self-renewal and pluri-differentiation; they are thought to play important roles in tumor initiation and maintenance. Stem-like cells in malignant glioma express CD133. We examined samples from human pituitary adenoma, a generally benign neoplasm, for CD133 expression using routine immunohistochemical and biochemical methods. Our study of 70 pituitary adenomas (clinically nonfunctioning adenomas and growth hormone-, prolactin-, adrenocorticotropic hormone-, and thyroid-stimulating hormone-producing adenomas) showed that 18 (25.7%) expressed CD133. This rate was higher in clinically nonfunctioning (33.3%) than functioning adenomas (12.0%) (p = 0.085). Real-time PCR assay revealed the expression of CD133 mRNA in samples immunohistochemically positive for CD133. Neither the patient age and gender, nor the tumor size or postoperative recurrence rate correlated with CD133 positivity. CD133+ cells ubiquitously coexpressed CD34, nestin, and VEGFR2 (KDL1). S-100 and GFAP were not coexpressed with CD133. Chromogranin A, Pit-1, SF-1, and NeuroD1 were immune-negative, indicating that CD133+ cells did not have the potential to differentiate into functional endocrine cells. Our data suggest that the expression of CD133 in pituitary adenomas is related to immature endothelial progenitor cells that may play a role in the neovascularization of pituitary adenomas. Further studies are needed to elucidate the significance of CD133+ cells with respect to neovascularization and their sustainable growth in pituitary adenomas.

Pituitary tumors contain a side population with tumor stem cell-associated characteristics

“…The endothelial-type SP cells of the pituitary tumors may represent a progenitor phenotype that drives angiogenesis during tumor expansion. The presence of endothelial progenitor cells in pituitary adenomas has indeed been suggested based on the detection of CD133, CD34, NESTIN, and VEGFR2 in non-hormonal and non-folliculostellate cells of the tumors (Yunoue et al 2011). Notably, the expression picture that was distilled from the total adenoma SP was found to be largely reconfirmed in the purified CD31 K /CD45 K SP (pSP).…”

The identification of human pituitary adenoma-initiating cells

“…A subset of tumors that are non-functional or do not secrete hormones are termed null cell (NC) adenomas [2]. While the multicellular milieu and hormonal subtypes of these tumors contribute to intra- and intertumoral heterogeneity, respectively, the initiation and maintenance of human PAs remains poorly understood [3, 19, 35, 36]. …”

Pituitary Stem Cells During Normal Physiology and Disease

“…However, progenitor cells or even differentiated cells could give rise to cells fulfilling CSC criteria upon transformation (Valent et al 2012;Clevers 2011). Several groups have reported the presence of putative CSCs in human pituitary adenomas and from mouse pituitary tumour models Xu et al 2009;Donangelo et al 2014;Lloyd et al 2013;Mertens et al 2015;Orciani et al 2015;van Rijn et al 2013;Yunoue et al 2011;Hosoyama et al 2010). It remains unknown if CSCs arise from PSCs, although their properties can be similar; for example, both are capable of in vitro self-renewal and differentiation and PSCs are likely to be chemoresistant like CSCs, since PSCs are found within the 'side population' generated by dye efflux, utilising the same transporter properties as chemoresistance (Chen et al 2009).…”