{"entity": "researcher", "timestamp": "2026-06-08T05:56:35.779Z", "family": "Welsh", "given": "Michael", "initials": "M", "orcid": "0000-0002-5467-9755", "affiliations": ["Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/c01673aeb9be429c80da30d5407b2725.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/c01673aeb9be429c80da30d5407b2725"}}, "publications": [{"entity": "publication", "iuid": "3026cc0df25b4c178a58bdb7ba158810", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3026cc0df25b4c178a58bdb7ba158810.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3026cc0df25b4c178a58bdb7ba158810"}}, "title": "Reduced vascular leakage correlates with breast carcinoma T regulatory cell infiltration but not with metastatic propensity.", "authors": [{"family": "He", "given": "Liqun", "initials": "L", "orcid": "0000-0002-4743-5410", "researcher": {"href": "https://publications.scilifelab.se/researcher/e6e2e4c7f88845bb895842e56a7622ae.json"}}, {"family": "Testini", "given": "Chiara", "initials": "C"}, {"family": "Hekmati", "given": "Neda", "initials": "N", "orcid": "0009-0009-4814-869X", "researcher": {"href": "https://publications.scilifelab.se/researcher/59e525846f61401ab94732e578190274.json"}}, {"family": "Bonello", "given": "Altea", "initials": "A"}, {"family": "Schiza", "given": "Aglaia", "initials": "A"}, {"family": "Nwadozi", "given": "Emmanuel", "initials": "E"}, {"family": "Phillipson", "given": "Mia", "initials": "M", "orcid": "0000-0002-2387-0266", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ebf9ffcab3e4a19add4c6dd51b727b1.json"}}, {"family": "Strell", "given": "Carina", "initials": "C", "orcid": "0000-0002-3783-7256", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb77b417ef2b479fb267969c3a557617.json"}}, {"family": "Welsh", "given": "Michael", "initials": "M", "orcid": "0000-0002-5467-9755", "researcher": {"href": "https://publications.scilifelab.se/researcher/c01673aeb9be429c80da30d5407b2725.json"}}], "type": "journal article", "published": "2025-10-16", "journal": {"title": "Mol Oncol", "issn": "1878-0261", "issn-l": "1574-7891"}, "abstract": "The vasculature and the immune system both play roles in breast cancer progression and metastasis. In an experimental mouse model of Shb-gene deficiency in endothelial cells, breast cancer lung metastasis correlated with immune suppression rather than with vascular leakage. The present study aimed to assess underlying gene expression changes in endothelial and immune cells responsible for this phenotype and to explore their relationship to human disease. Mouse endothelial cell Shb-gene deficiency, leading to 'vessel normalization', resulted in altered expression of chemo/cytokine genes and upregulation of immune checkpoint genes in immune cells. Endothelial cells under these conditions exhibited gene expression patterns compatible with reduced angiogenesis and vascular leakage. Additionally, genes whose products relate to immune cell vascular transmigration and function were affected. In a human triple-negative breast cancer cohort, tumors with reduced vascular leakage exhibited a higher relative proportion of regulatory T cells and larger tumor size. However, these changes were not associated with increased metastasis. In conclusion, a low leakage vascular phenotype reduces tumor cell intravasation/metastasis and modifies the immune response, which in the current context becomes pro-tumoral.", "doi": "10.1002/1878-0261.70144", "pmid": "41102920", "labels": {"National Genomics Infrastructure": "Service", "NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-07T07:23:33.643Z", "modified": "2025-11-13T17:36:03.258Z"}, {"entity": "publication", "iuid": "a0dda33b98ee48789e7ac7a800a80bb5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a0dda33b98ee48789e7ac7a800a80bb5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a0dda33b98ee48789e7ac7a800a80bb5"}}, "title": "Pericyte dysfunction due to Shb gene deficiency increases B16F10 melanoma lung metastasis.", "authors": [{"family": "He", "given": "Qi", "initials": "Q"}, {"family": "Li", "given": "Xiujuan", "initials": "X"}, {"family": "He", "given": "Liqun", "initials": "L"}, {"family": "Li", "given": "Yousheng", "initials": "Y"}, {"family": "Betsholtz", "given": "Christer", "initials": "C"}, {"family": "Welsh", "given": "Michael", "initials": "M", "orcid": "0000-0002-5467-9755", "researcher": {"href": "https://publications.scilifelab.se/researcher/c01673aeb9be429c80da30d5407b2725.json"}}], "type": "journal article", "published": "2020-11-01", "journal": {"title": "Int. J. Cancer", "issn": "1097-0215", "volume": "147", "issue": "9", "pages": "2634-2644", "issn-l": "0020-7136"}, "abstract": "Intravasation, vascular dissemination and metastasis of malignant tumor cells require their passage through the vascular wall which is commonly composed of pericytes and endothelial cells. We currently decided to investigate the relative contribution of these cell types to B16F10 melanoma metastasis in mice using an experimental model of host Shb gene (Src homology 2 domain-containing protein B) inactivation. Conditional inactivation of Shb in endothelial cells using Cdh5-CreERt2 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 Shb in pericytes using Pdgfrb-CreERt2 resulted in decreased pericyte coverage of small tumor vessels with lumen, increased leakage, aberrant platelet-derived 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 Shb deficiency. It is concluded that proper pericyte function plays a significant role in suppressing B16F10 lung metastasis.", "doi": "10.1002/ijc.33110", "pmid": "32441314", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-08T23:56:20.495Z", "modified": "2024-01-16T13:48:41.445Z"}]}