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We currently decided to investigate the relative contribution of these cell types to B16F10 melanoma metastasis in mice using an experimental model of host <jats:italic>Shb<\/jats:italic> gene (Src homology 2 domain\u2010containing protein B) inactivation. Conditional inactivation of <jats:italic>Shb<\/jats:italic> in endothelial cells using <jats:italic>Cdh5\u2010CreERt2<\/jats:italic> resulted in decreased tumor growth, reduced vascular leakage, increased hypoxia and no effect on pericyte coverage and lung metastasis. RNAseq of tumor endothelial cells from these mice revealed changes in cellular components such as adherens junctions and focal adhesions by gene ontology analysis that were in line with the observed effects on leakage and junction morphology. Conditional inactivation of <jats:italic>Shb<\/jats:italic> in pericytes using <jats:italic>Pdgfrb\u2010CreERt2<\/jats:italic> resulted in decreased pericyte coverage of small tumor vessels with lumen, increased leakage, aberrant platelet\u2010derived growth factor receptor B (PDGFRB) signaling and a higher frequency of lung metastasis without concomitant effects on tumor growth or oxygenation. Flow cytometry failed to reveal immune cell alterations that could explain the metastatic phenotype in this genetic model of <jats:italic>Shb<\/jats:italic> deficiency. It is concluded that proper pericyte function plays a significant role in suppressing B16F10 lung metastasis.<\/jats:p>","DOI":"10.1002\/ijc.33110","type":"journal-article","created":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T09:59:15Z","timestamp":1590141555000},"page":"2634-2644","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pericyte dysfunction due to <i>Shb<\/i> gene deficiency increases <scp>B16F10<\/scp> melanoma lung metastasis"],"prefix":"10.1002","volume":"147","author":[{"given":"Qi","family":"He","sequence":"first","affiliation":[{"name":"Department of Medical Cell Biology Uppsala University  Uppsala Sweden"},{"name":"Research Institute of General Surgery, Jinling Hospital, School of Medicine Nanjing University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiujuan","family":"Li","sequence":"additional","affiliation":[{"name":"Cyrus Tang Hematology Center, 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