Expression of Chemokine CXCL12 and Its Receptor CXCR4 in Folliculostellate (FS) Cells of the Rat Anterior Pituitary Gland: The CXCL12/CXCR4 Axis Induces Interconnection of FS Cells

Abstract

The anterior pituitary gland is composed of five types of hormone-producing cells plus folliculostellate (FS) cells, which do not produce classical anterior pituitary hormones. FS cells are interconnected by cytoplasmic processes and encircle hormone-producing cells or aggregate homophilically. Using living-cell imaging of primary culture, we recently reported that some FS cells precisely extend their cytoplasmic processes toward other FS cells and form interconnections with them. These phenomena suggest the presence of a chemoattractant factor that facilitates the interconnection. In this study, we attempted to discover the factor that induces interconnection of FS cells and succeeded in identifying chemokine (CXC)-L12 and its receptor CXCR4 as potential candidate molecules. CXCL12 is a chemokine of the CXC subfamily. It exerts its effects via CXCR4, a G protein-coupled receptor. The CXCL12/CXCR4 axis is a potent chemoattractant for many types of neural cells. First, we revealed that CXCL12 and CXCR4 are expressed by FS cells in rat anterior pituitary gland. Next, to clarify the function of the CXCL12/CXCR4 axis in FS cells, we observed living anterior pituitary cells in primary culture with specific CXCL12 inhibitor or CXCR4 antagonist and noted that extension of cytoplasmic processes and interconnection of FS cells were inhibited. Finally, we examined FS cell migration and invasion by using Matrigel matrix assays. CXCL12 treatment resulted in markedly increased FS cell migration and invasion. These data suggest that FS cells express chemokine CXCL12 and its receptor CXCR4 and that the CXCL12/CXCR4 axis evokes interconnection of FS cells.

CXCR4 antagonist inhibits perineural invasion of adenoid cystic carcinoma

“…The striking difference in expression levels of CXCR4 between ACC and HNSCC could account for the distinct features regarding neurotropism. In this context, data support the role of CXCR4 in neural invasion in a number of recent elaborate studies 3 4…”

Pituitary Stem Cells: Quest for Hidden Functions

“…Of interest, SOX2, OCT4, NANOG and KLF4 constitute the transcription-factor core of embryonic stem (ES) and induced pluripotent stem (iPS) cells, the prototypical stem cells (De Los Angeles et al 2015;Hyslop et al 2005;Takahashi and Yamanaka 2006). Finally, the chemotactic receptor CXCR4 (C-X-C chemokine receptor type 4), which is more and more classified as a general stemness marker, is also upregulated in the pituitary stem cell compartment (Horiguchi et al 2012;Vankelecom 2010Vankelecom , 2012Vankelecom and Chen 2014).…”

Stem Cells in Neuroendocrinology

“…Of interest, SOX2, OCT4, NANOG and KLF4 constitute the transcription-factor core of embryonic stem (ES) and induced pluripotent stem (iPS) cells, the prototypical stem cells (De Los Angeles et al 2015;Hyslop et al 2005;. Finally, the chemotactic receptor CXCR4 (C-X-C chemokine receptor type 4), which is more and more classified as a general stemness marker, is also upregulated in the pituitary stem cell compartment (Horiguchi et al 2012;Vankelecom , 2012Vankelecom and Chen 2014).…”