Apolipoprotein D is crucial for promoting perineural invasion in salivary adenoid cystic carcinoma
- Br J Cancer. 2025 Feb 17. doi: 10.1038/s41416-025-02946-1.
- 1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
- 2. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
- 3. Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, 100081, Beijing, China.
- 4. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
- 5. Department of Dentistry, The Second People's Hospital of Tibet Autonomous Region, Xizang, 850030, China.
- 6. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & Department of Anesthesiology, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
- 7. Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China.
- 8. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China. [email protected].
- 9. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China. [email protected].
- # Contributed equally.
Background: Perineural invasion (PNI) is a prevalent phenomenon in salivary adenoid cystic carcinoma (SACC). Nevertheless, the regulatory mechanism of PNI is largely elusive.
Methods: We detected Apolipoprotein D (ApoD) expression and further determined its role in SACC progression. Subsequently, the contributions of SACC-derived ApoD on neurite outgrowth of dorsal root ganglions (DRGs) cells were explored. Moreover, a series of in vivo assays were conducted to elucidate the role of ApoD in the SACC PNI process.
Results: We observed a dramatic up-regulation of ApoD in the SACC associated with an enhancement of PNI in patient biopsies. We found that SACC-derived ApoD elevated Cancer cell migration and invasion. In addition, ApoD could facilitate the neurite outgrowth of cultured DRG cells in a CXCR4-dependent manner in vitro, as well as innervation, angiogenesis, and invasion along peripheral nerves of SACC in vivo. More importantly, by advanced bioinformatic analysis, we unexpectedly revealed a novel phenomenon 'tumour cell to neuron-like cell transition' in the ApoD-rich microenvironment in vivo, contributing to the neurogenesis in the SACC tumour.
Conclusion: we discovered a novel role of cancer-derived ApoD in the pathogenesis of PNI, which may represent an effective therapeutic target for SACC in clinics.