Single-cell sequencing reveals MCAM+ MyCAFs as key pro-angiogenic cells interacting with endothelial cells in solid-type adenoid cystic carcinoma

Compared to non-solid-type ACC, CAFs in solid-type ACC are predominantly composed of melanoma cell adhesion molecule (MCAM)⁺ myofibroblastic cancer-associated fibroblasts (myCAFs). The transcriptional levels of pro-angiogenic factors such as platelet-derived growth factor subunit A (PDGFA), platelet-derived growth factor subunit B (PDGFB), angiopoietin-1 (ANGPT1), and angiopoietin-2 (ANGPT2) in MCAM⁺ myCAFs were significantly upregulated and exhibited stronger pro-angiogenic activity than MCAM^- fibroblasts from non-solid-type ACC. In vivo experiments showed that MCAM⁺ myCAFs mixed with the ACC cell line salivary gland adenoid cystic carcinoma cell line 83 (SACC83) had a stronger tumorigenic ability and induced more abundant microvascular formation compared to the implantation of SACC83 alone. Additionally, the transcription factor myocyte enhancer factor 2 C (MEF2C) was found to bind to the promoters of PDGFA, PDGFB, ANGPT1, and ANGPT2, initiating their transcription. Knockdown of MEF2C inhibited the pro-angiogenic activity of MCAM⁺ myCAFs both in vitro and in vivo CONCLUSION: MCAM⁺ myCAFs promote the transcription of pro-angiogenic factors through MEF2C, thereby enhancing angiogenesis and promoting tumor growth in solid-type ACC.