Biology subjects

Span, P. N.

Publications and source records attributed to Span, P. N..

2 recordsLinked to original sources

bioRxiv2020

Transcriptional comparison of Testicular Adrenal Rest Tumors with fetal and adult tissues

Testicular Adrenal Rest Tumors (TART) are a common complication of unknown origin in patients with Congenital Adrenal Hyperplasia. These benign tumors may derive from cells of adrenal origin or from pluripotent progenitor cells from the fetal adrenogonadal primordium. By comparing the transcriptome of TART with fetal- and adult-testis and adrenal tissues, this study aims to unravel the origin of TART. Targeted transcriptome sequencing was followed by unsupervised clustering-, differential expression-, functional enrichment- and pathway analyses. Immunohistochemistry demonstrated co-expression of adrenal-specific CYP11B1 and testis-specific HSD17B3 in TART, indicating the existence of a distinct TART cell exhibiting both adrenal- and testicular characteristics. Principal component analysis indicated that the TART transcriptome was distinct from either adrenal or testis fetal tissue, making a progenitor-like phenotype of TART unlikely. Rather, TART appears to originate from -or differentiate into-a mature cell type, with both adrenal- and testicular characteristics. The present study, the first to describe the TART transcriptome, expands knowledge about the identity and functional characteristics of TART and identifies clinically targetable pathways associated with fibrosis.

molecular biology↗

bioRxiv2019

Leader cell activity and collective invasion by an autocrine nucleotide loop through connexin-43 hemichannels and ADORA1

Progression of epithelial cancers predominantly proceeds by collective invasion of cell groups with coordinated cell-cell junctions and multicellular cytoskeletal activity. Collectively invading breast cancer cells co-express adherens junctions and connexin-43 (Cx43) gap junctions in vitro and in patient samples, yet whether gap junctions contribute to collective invasion remains unclear. We here show that Cx43 is required for chemical coupling between collectively invading breast cancer cells and, by its hemichannel function, adenosine nucleotide release into the extracellular space. Using molecular interference and rescue strategies in vitro and in orthotopic mammary tumors in vivo, Cx43-dependent adenosine nucleotide release was identified as essential mediator engaging the nucleoside receptor ADORA1, to induce leader cell activity and collective migration. In clinical samples joint-upregulation of Cx43 and ADORA1 predicts decreased relapse-free survival. This identifies autocrine nucleotide signaling, through a Cx43/ADORA1 axis, as critical pathway in leader cell function and collective cancer cell invasion. Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

cancer biology↗