{"entity": "publication", "iuid": "0764d6ec647143f5b4ee9d7a61c6132e", "timestamp": "2026-05-09T17:54:20.896Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0764d6ec647143f5b4ee9d7a61c6132e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0764d6ec647143f5b4ee9d7a61c6132e"}}, "title": "Transforming growth factor-\u03b2 signalling controls human breast cancer metastasis in a zebrafish xenograft model.", "authors": [{"family": "Drabsch", "given": "Yvette", "initials": "Y"}, {"family": "He", "given": "Shuning", "initials": "S"}, {"family": "Zhang", "given": "Long", "initials": "L"}, {"family": "Snaar-Jagalska", "given": "B Ewa", "initials": "BE"}, {"family": "ten Dijke", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2013-11-07", "journal": {"title": "Breast Cancer Res.", "issn": "1465-542X", "volume": "15", "issue": "6", "pages": "R106", "issn-l": "1465-5411"}, "abstract": "The transforming growth factor beta (TGF-\u03b2) signalling pathway is known to control human breast cancer invasion and metastasis. We demonstrate that the zebrafish xenograft assay is a robust and dependable animal model for examining the role of pharmacological modulators and genetic perturbation of TGF-\u03b2 signalling in human breast tumour cells.\n\nWe injected cancer cells into the embryonic circulation (duct of cuvier) and examined their invasion and metastasis into the avascular collagenous tail. Various aspects of the TGF-\u03b2 signalling pathway were blocked by chemical inhibition, small interfering RNA (siRNA), or small hairpin RNA (shRNA). Analysis was conducted using fluorescent microscopy.\n\nBreast cancer cells with different levels of malignancy, according to in vitro and in vivo mouse studies, demonstrated invasive and metastatic properties within the embryonic zebrafish model that nicely correlated with their differential tumourigenicity in mouse models. Interestingly, MCF10A M2 and M4 cells invaded into the caudal hematopoietic tissue and were visible as a cluster of cells, whereas MDA MB 231 cells invaded into the tail fin and were visible as individual cells. Pharmacological inhibition with TGF-\u03b2 receptor kinase inhibitors or tumour specific Smad4 knockdown disturbed invasion and metastasis in the zebrafish xenograft model and closely mimicked the results we obtained with these cells in a mouse metastasis model. Inhibition of matrix metallo proteinases, which are induced by TGF-\u03b2 in breast cancer cells, blocked invasion and metastasis of breast cancer cells.\n\nThe zebrafish-embryonic breast cancer xenograft model is applicable for the mechanistic understanding, screening and development of anti-TGF-\u03b2 drugs for the treatment of metastatic breast cancer in a timely and cost-effective manner.", "doi": "10.1186/bcr3573", "pmid": "24196484", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "bcr3573"}, {"db": "pmc", "key": "PMC3978640"}], "notes": [], "created": "2018-12-05T08:59:03.817Z", "modified": "2018-12-05T08:59:03.849Z"}