1282 Basal cell carcinoma pigmentation is associated with melanocyte proliferation and expression of the melanocyte mitogens endothelin 1 and 2 by tumor cells

Basal cell carcinoma (BCC) is the most common cutaneous malignancy and characterized by sustained Hedgehog (Hh) signaling. Despite major insights into molecular basis of BCC, relatively little known about how BCC tumor cells affect other types in microenvironment. It has been frequently observed that a subset tumors are clinically pigmented. Using immunostaining for melanocyte-specific antigens, we found human mouse BCCs contain nodules with abundant proliferating melanocytes, even not grossly We performed single-cell RNA sequencing to search potential tumor-cell derived factors capable driving melanocyte proliferation. expression potent mitogens Endothelins 1 2 (Edn1, Edn2) was markedly upregulated cells, whereas corresponding Endothelin receptor type B (Ednrb) largely restricted melanocytes. Conditioned medium from BCC-like but squamous or normal keratinocytes, stimulated proliferation cultured Moreover, proliferative response melanocytes conditioned completely blocked small-molecule EDNRB inhibitor. Finally, biopsies obtained patient before during treatment Hh pathway inhibitor vismodegib, regression correlated reduced apoptosis tumor-associated Taken together, our data identify as frequent inhabitants microenvironment, point Edn1 and/or Edn2 likely tumor-cell-derived factor(s) may explain well-known poorly understood propensity pigmentation BCCs.