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

Melanoma/drug therapy*
Melanoma/immunology
Bacterial Proteins/administration & dosage*
Bacterial Proteins/immunology
Xenograft Model Antitumor Assays
Cell Line, Tumor
Macrophages/metabolism*
Cell Polarity/drug effects
Cell Proliferation/drug effects
Cell Survival/drug effects
Zebrafish
Animals
Neoplasm Metastasis

PubMed

35163566 Full text @ Int. J. Mol. Sci.

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.

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