{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T06:56:43Z","timestamp":1770706603090,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Veneto Institute of Oncology IOV","award":["DE_B_EPPR19_02 - IOV 5x1000 \u201cMETAMELAHP-NAP\u201d"],"award-info":[{"award-number":["DE_B_EPPR19_02 - IOV 5x1000 \u201cMETAMELAHP-NAP\u201d"]}]},{"DOI":"10.13039\/501100007076","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["IG-2017-19928"],"award-info":[{"award-number":["IG-2017-19928"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["MFAG 2019\u2014ID. 23192"],"award-info":[{"award-number":["MFAG 2019\u2014ID. 23192"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Telethon Foundation","doi-asserted-by":"publisher","award":["GGP19287"],"award-info":[{"award-number":["GGP19287"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms23031644","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T08:20:29Z","timestamp":1643617229000},"page":"1644","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Macrophage-Mediated Melanoma Reduction after HP-NAP Treatment in a Zebrafish Xenograft Model"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7793-2549","authenticated-orcid":false,"given":"Gaia","family":"Codolo","sequence":"first","affiliation":[{"name":"Department of Biology, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Facchinello","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Padova, 35121 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9799-9022","authenticated-orcid":false,"given":"Nicole","family":"Papa","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35131 Padova, Italy"},{"name":"Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ambra","family":"Bertocco","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Coletta","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9077-2471","authenticated-orcid":false,"given":"Clara","family":"Benna","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35124 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1564-2594","authenticated-orcid":false,"given":"Luigi","family":"Dall\u2019Olmo","sequence":"additional","affiliation":[{"name":"Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padova, Italy"},{"name":"Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35124 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Mocellin","sequence":"additional","affiliation":[{"name":"Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padova, Italy"},{"name":"Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35124 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5444-9853","authenticated-orcid":false,"given":"Natascia","family":"Tiso","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0091-4502","authenticated-orcid":false,"given":"Marina","family":"de Bernard","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1080\/15384047.2019.1640032","article-title":"Current State of Melanoma Diagnosis and Treatment","volume":"20","author":"Davis","year":"2019","journal-title":"Cancer Biol. 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