2. Academic Validation
  3. Apolipoprotein D is crucial for promoting perineural invasion in salivary adenoid cystic carcinoma

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.
Guangzhao Huang # 1,  Su Chen # 1,  Bo Han # 1,  Gaowei Zhang 2,  Mingzhe Bao 1,  Grace Paka Lubamba 1,  Yufei Hua 1,  Honglin Li 1,  Wenwen Liu 3,  Jiefei Shen 4,  Lei Wang 5,  Jie Lin 6,  Patrick Ming-Kuen Tang 7,  Zhangfan Ding 8,  Chunjie Li 9
Affiliations

Affiliations

  • 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. dingzf16@163.com.
  • 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. lichunjie@scu.edu.cn.
  • # Contributed equally.
PMID: 39962257 DOI: 10.1038/s41416-025-02946-1
Abstract

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.

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