SFRP1 mediates cancer-associated fibroblasts to suppress cancer cell proliferation and migration in head and neck squamous cell carcinoma.

ABSTRACT

BACKGROUND: Cancer-associated fibroblasts (CAFs), as key cell populations in the tumor microenvironment (TME), play a crucial role in tumor regulation. Previous studies on a prognostic signature of 8 CAF-related genes in head and neck squamous cell carcinoma (HNSCC) revealed that Secreted frizzled-related protein 1 (SFRP1) is one of the hub genes closely related to CAFs. SFRP1 is deficiently expressed in numerous types of cancer and is classified as a tumor suppressor gene. However, the role of SFRP1 in TME regulation in HNSCC remains unclear. This study aimed to explore the role of SFRP1 in the proliferation and migration of HNSCC cells by mediating CAFs and their regulatory mechanisms. METHODS: The expression differences, prognosis, and immune infiltration of SFRP1 in HNSCC were analyzed using the TIMER and GEPIA2 databases. The expression of SFRP1 in HNSCC tumor tissues, as well as the expression and secretion of SFRP1 in CAFs and tumor cells, were examined. An indirect co-culture system was constructed to detect the proliferation, migration, and apoptosis of HNSCC cells, and to clarify the effect of SFRP1 on tumor cells by mediating CAFs. Furthermore, the expression and secretion of 10 cytokines derived from CAFs that act on immune cells were verified. RESULTS: SFRP1 was differently expressed in HNSCC tumor tissues and highly expressed in CAFs. SFRP1 inhibited the proliferation and migration of tumor cells and promoted apoptosis by mediating CAFs. The detection of CAFs-derived factors suggested that the mechanism of action of SFRP1 was associated with the regulation of immune cells. CONCLUSION: SFRP1 inhibits the proliferation and migration of HNSCC cells by mediating CAFs, and the mechanism of action is related to the regulation of immune cells, which may provide new research directions and therapeutic targets for HNSCC.