{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:53:21Z","timestamp":1790931201640,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Nestin\u2010expressing stem cells located in the bulge area of the hair follicle can give rise to multiple cell types. In the present study, we subcutaneously transplanted red fluorescent protein (RFP)\u2010labeled SK\u2010MEL\u20105 human melanoma cells into nestin\u2010driven green fluorescent protein (ND\u2010GFP)\u2010nude mice. Nestin\u2010GFP\u2010positive cells differentiated into CD31\u2010positive endothelial cells and \u03b1SMA\u2010positive pericytes, and \u03b2III\u2010tubulin\u2010positive neurons, forming blood vessel\u2010like and nerve\u2010like structures within the transplanted melanoma. Bevacizumab, a vascular endothelial growth factor (VEGF)\u2010targeting monoclonal antibody, suppressed nestin\u2010positive blood\u2010vessel structures and nerve structures from forming within the tumor but did not significantly inhibit tumor growth. Due to bevacizumab treatment, blood\u2010vessel\u2010like and nerve\u2010like structures expressing CD31, \u03b1SMA, and \u03b2III tubulin formed without the expression of nestin in the transplanted melanoma but remained RFP\u2010positive, suggesting that they trans\u2010differentiated from melanoma cells. Relative mRNA expression of VEGFA also significantly decreased in the melanoma after bevacizumab treatment of the mice. In contrast, VEGFR2 and FGF6, markers that are related to blood vessels, significantly increased compared with the non\u2010treated mice. In the bevacizumab\u2010treated mice, mRNA expression of Tuj1, BDNF, and IGF1 markers related to nerves significantly increased within the melanoma. In the bevacizumab\u2010treated mice, nestin expression was not detected, but RFP was maintained in the blood\u2010vessel\u2010like and nerve\u2010like structures in the melanoma. Since nestin was not detected and RFP was maintained, it suggests these structures trans\u2010differentiated from the melanoma cells. The present study suggests that both the host and cancer cells can differentiate into blood\u2010vessel\u2010like and nerve\u2010like structures in the melanoma.<\/jats:p>","DOI":"10.1111\/cas.70441","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:08:02Z","timestamp":1785755282000},"page":"2790-2802","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Melanoma Transplanted in Nude Mice Has Both Host\u2010 and Tumor\u2010Derived Blood Vessel\u2010 and Nerve\u2010Like Structures"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5235-3161","authenticated-orcid":false,"given":"Koya","family":"Obara","sequence":"first","affiliation":[{"name":"AntiCancer, Inc.  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