Exosomal Sonic Hedgehog derived from cancer-associated fibroblasts promotes proliferation and migration of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common and aggressive malignancies in China. Cancer-associated fibroblasts (CAFs) can actively communicate with and stimulate tumor cells, thereby contributing to the development and progression of tumors. Yet, whether CAFs-derived exosomes have a role in the progression of ESCC is largely unknown. Here, we find that Sonic Hedgehog (SHH) is highly expressed in CAFs lysis solution, conditioned medium of cultured CAFs (CAF-CM) and CAFs-derived exosomes, and esophageal cancer cell lines educated by CAF-CM and CAFs-derived exosomes can improve their growth and migration abilities in vitro and in vivo. Besides, those effects can be partly neutralized by cyclopamine, inhibitor of the Hedgehog signaling pathway. Thus, our research elucidates the crucial role of CAFs-derived exosomes in the growth and progression of ESCC, and may open up new avenues in the treatment of ESCC.