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Updated: Jun 16, 2025
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Targeting the VIP-VPAC Pathway in Melanoma Models Inhibits Tumor Growth and Liver Metastasis.
Wenxi Wang1, Hua Yang2, Tenzin Passang3
1Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA; Department of Oncology, Xiangya Hospital, Central South University (CSU), Changsha, China; Department of Radiation Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center, China.
Vasoactive intestinal peptide (VIP) receptor signaling drives liver metastasis in uveal melanoma (UVM). A novel antagonist, ANT308, reduced melanoma spread and may offer a new therapeutic strategy for metastatic UVM.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Uveal melanoma (UVM) has poor outcomes due to resistance to therapies and frequent liver metastases.
- Vasoactive intestinal peptide (VIP) signaling is an immune checkpoint in pancreatic cancer but its role in melanoma is unknown.
Purpose of the Study:
- To investigate the role of VIP receptor signaling in melanoma progression and metastasis.
- To evaluate the efficacy of a novel VIP receptor antagonist, ANT308, in preclinical melanoma models.
Main Methods:
- In vitro studies using murine and human melanoma cell lines to assess effects on cell migration and proliferation.
- RNA sequencing and Western blot analyses to determine molecular mechanisms.
- In vivo studies in murine models to evaluate ANT308's impact on primary tumor growth and liver metastasis.
Main Results:
- ANT308 inhibited VIP receptor signaling, reducing melanoma cell migration and proliferation in vitro.
- ANT308 downregulated melanoma cell adhesion molecule (MCAM) and N-cadherin expression.
- In vivo, ANT308 decreased MCAM expression, reduced liver metastases, and showed a trend toward reduced primary tumor volume.
Conclusions:
- VIP receptor signaling promotes liver metastasis in melanoma.
- Targeting VIP receptor signaling with antagonists like ANT308 may be a novel therapeutic strategy for metastatic UVM.
