PUBLICATION
Macrophage-Mediated Melanoma Reduction after HP-NAP Treatment in a Zebrafish Xenograft Model
- Authors
- Codolo, G., Facchinello, N., Papa, N., Bertocco, A., Coletta, S., Benna, C., Dall'Olmo, L., Mocellin, S., Tiso, N., de Bernard, M.
- ID
- ZDB-PUB-220216-16
- Date
- 2022
- Source
- International Journal of Molecular Sciences 23(3): (Journal)
- Registered Authors
- Facchinello, Nicola, Tiso, Natascia
- Keywords
- HP-NAP, macrophages, melanoma, zebrafish
- MeSH Terms
-
- Animals
- Bacterial Proteins/administration & dosage*
- Bacterial Proteins/immunology
- Cell Line, Tumor
- Cell Polarity/drug effects
- Cell Proliferation/drug effects
- Cell Survival/drug effects
- Macrophages/metabolism*
- Melanoma/drug therapy*
- Melanoma/immunology
- Neoplasm Metastasis
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 35163566 Full text @ Int. J. Mol. Sci.
Citation
Codolo, G., Facchinello, N., Papa, N., Bertocco, A., Coletta, S., Benna, C., Dall'Olmo, L., Mocellin, S., Tiso, N., de Bernard, M. (2022) Macrophage-Mediated Melanoma Reduction after HP-NAP Treatment in a Zebrafish Xenograft Model. International Journal of Molecular Sciences. 23(3):.
Abstract
The Helicobacter pylori Neutrophil Activating Protein (HP-NAP) is endowed with immunomodulatory properties that make it a potential candidate for anticancer therapeutic applications. By activating cytotoxic Th1 responses, HP-NAP inhibits the growth of bladder cancer and enhances the anti-tumor activity of oncolytic viruses in the treatment of metastatic breast cancer and neuroendocrine tumors. The possibility that HP-NAP exerts its anti-tumor effect also by modulating the activity of innate immune cells has not yet been explored. Taking advantage of the zebrafish model, we examined the therapeutic efficacy of HP-NAP against metastatic human melanoma, limiting the observational window to 9 days post-fertilization, well before the maturation of the adaptive immunity. Human melanoma cells were xenotransplanted into zebrafish embryos and tracked in the presence or absence of HP-NAP. The behavior and phenotype of macrophages and the impact of their drug-induced depletion were analyzed exploiting macrophage-expressed transgenes. HP-NAP administration efficiently inhibited tumor growth and metastasis and this was accompanied by strong recruitment of macrophages with a pro-inflammatory profile at the tumor site. The depletion of macrophages almost completely abrogated the ability of HP-NAP to counteract tumor growth. Our findings highlight the pivotal role of activated macrophages in counteracting melanoma growth and support the notion that HP-NAP might become a new biological therapeutic agent for the treatment of metastatic melanomas.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping