2. Academic Validation
  3. VGF-Derived TLQP-21 Ameliorates Tumor Progression, Pain, and Depression-Like Behaviors in an Orthotopic Mouse Model of Pancreatic Ductal Adenocarcinoma

VGF-Derived TLQP-21 Ameliorates Tumor Progression, Pain, and Depression-Like Behaviors in an Orthotopic Mouse Model of Pancreatic Ductal Adenocarcinoma

  • FASEB J. 2025 Jul 31;39(14):e70802. doi: 10.1096/fj.202500400R.
Shuying Huang 1,  Pei Xia 1 2,  Qiuyi Chen 1,  Yixiu Zeng 1,  Xin Cheng 1,  Qianyi Cao 1,  Wenbao Cai 1,  Yuying Yang 1,  Yang Ouyang 1,  Xinyu Wang 3 4 5,  Yiyi Li 3 4 5,  Jun Chen 3 4 5,  Wei-Jye Lin 6 7 8,  Xiaojing Ye 1
Affiliations

Affiliations

  • 1 Faculty of Forensic Medicine, Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 2 Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China.
  • 3 Department of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 4 Guangdong Engineering & Technology Research Center for Disease-Model Animals, Laboratory Animal Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 5 Key Laboratory of Tropical Disease Control of the Ministry of Education, Sun Yat-sen University, Guangzhou, China.
  • 6 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
  • 7 Brain Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
  • 8 Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Foshan, China.
PMID: 40654186 DOI: 10.1096/fj.202500400R
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive Cancer associated with severe pain and depression. Neuropeptide VGF (non-acronymic) exhibits robust expression in the pancreas and brain, known for its modulatory roles in metabolic homeostasis, nociception, and depression-like behaviors. Despite elevated VGF expression being linked to poor prognosis in various cancers, its specific role in PDAC remains unexplored. By combining bioinformatic analysis of clinical datasets with experimental validations, we uncover that high VGF expression correlates with improved survival in PDAC patients. Notably, the administration of TLQP-21, a C-terminal peptide derived from VGF, significantly reduces tumor size and enhances the therapeutic efficacy of gemcitabine, resulting in a marked increase in overall survival in an orthotopic mouse model of PDAC. Mechanistically, TLQP-21 suppresses the tumor-promoting effects of tumor-associated macrophages through complement receptors C3aR1 and C1qBP. Additionally, TLQP-21 alleviates depression-like behaviors, allodynia, and muscle wasting in PDAC mice. Collectively, these findings demonstrate the dual efficacy of TLQP-21 in inhibiting tumor growth and mitigating nociceptive and psychiatric symptoms, highlighting the potential of TLQP-21 as a therapeutic option for PDAC.

Keywords

VGF; depression‐like behaviors; macrophages; pain; pancreatic ductal adenocarcinoma.

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