Cancer Associated fibroblast profiling reveals endothelin signalling as a novel mediator of niche to tumor cross-talk in Basal Cell Carcinoma

ABSTRACT: Basal Cell Carcinoma (BCC) is known to rely heavily on interactions with its niche but little is understood regarding how the various cell types interact. In order to determine specifically how the Cancer associated fibroblasts (CAFs) in the BCC niche impact tumor development we have undertaken cell type specific RNA sequencing and have identified signalling mechanisms within and between compartments that mediate BCC development. Using very early stage BCC we have determined that CAF changes occur early, and we have shown that CAFs evolve over time during the tumors development. Adhesion and metabolic alterations early in tumor development progress to immune system regulators becoming more pronounced later in the process. Specifically, we have identified that Endothelin ligand from keratinoctyes promotes Endothelin signalling in fibroblasts, and that this signalling is crucial for BCC growth. Using cell type specific analyses we have dissected the intercompartmental signalling necessary for BCC development, and identified candidate signalling networks essential for tumor growth. This work not only provides meaningful candidates but also validates that changes in CAFs are essential facilitators of BCC development, from early in tumor development. Overall design: RNA sequencing of matched CD26+ve fibroblasts and EPCAM+ve keratinocyte samples from murine inducible Basal Cell Carcinoma

INSTRUMENT(S): Illumina NextSeq 500 (Mus musculus)

ORGANISM(S): Mus Musculus

SUBMITTER: Kiarash Khosrotehrani  

PROVIDER: GSE122571 | GEO | 2019-12-01

REPOSITORIES: GEO