Cutaneous squamous cell carcinoma (cSCC) is the second prevalent form of skin cancer, showing a rapidly increasing incidence worldwide. In the skin, neurotrophins and their receptors (CD271 and Trks) form a complex network regulating epidermal homeostasis. CD271 is implicated in the switch between stem and early progenitors, thus playing a key role in keratinocyte differentiation. However, its role in cSCC is still to be defined. We observed that CD271 overexpression reduced growth and invasion of cSCC cell line-derived spheroids by promoting tumor differentiation. In fact, by RNAseq analysis, we found a significant fold-enrichment of genes involved in epidermal cell differentiation in CD271-overexpressing vs mock spheroids. Interestingly, CD271 expression increases from actinic keratosis to well-differentiated (WD) cSCC, while it is slightly or not expressed in mild/poorly differentiated primary tumors (MD/PD). Starting from cSCC biopsies, we generated patient-derived spheroids, thus obtaining a 3D model reflecting several degrees of cSCC aggressiveness. We found a higher mRNA level of CD271 in WD-spheroids and of TrkA in MD/PD-spheroids, which also express the highest levels of Survivin and IL-8. Importantly, CD271 overexpression in MD-spheroids significantly reduced cell proliferation and spheroids area. Furthermore, we developed a novel patients-derived xenograft zebrafish model, by using both lysC::DsRED2 and mpeg1::mCherry transgenic zebrafish lines. The grafting of CD271-overexpressing cells resulted in a significantly lower metastatic capacity and promoted the recruitment of macrophages within the site of injection. Therefore, our results indicate an inverse correlation between CD271 expression and malignancy level and CD271 could potentially have a role in the switch between the less aggressive to the high-risk cSCC.

ESDR438 - CD271 modulates cutaneous squamous cell carcinoma growth and invasion in patient-derived spheroids and zebrafish avatar

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.