دورية أكاديمية
أعرض في EDS

Epithelial requirement for in vitro proliferation and xenograft growth and metastasis of MDA-MB-468 human breast cancer cells: oncogenic rather than tumor-suppressive role of E-cadherin.

التفاصيل البيبلوغرافية
العنوان: Epithelial requirement for in vitro proliferation and xenograft growth and metastasis of MDA-MB-468 human breast cancer cells: oncogenic rather than tumor-suppressive role of E-cadherin.
المؤلفون: Hugo HJ; Invasion and Metastasis Unit, St. Vincent's Institute, Melbourne, VIC, Australia. honor.hugo@qut.edu.au.; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. honor.hugo@qut.edu.au.; School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia. honor.hugo@qut.edu.au.; Translational Research Institute, Woolloongabba, QLD, Australia. honor.hugo@qut.edu.au., Gunasinghe NPAD; Invasion and Metastasis Unit, St. Vincent's Institute, Melbourne, VIC, Australia., Hollier BG; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.; Australian Prostate Cancer Research Centre-Queensland, Brisbane, Australia., Tanaka T; Translational Research Institute, Woolloongabba, QLD, Australia., Blick T; Invasion and Metastasis Unit, St. Vincent's Institute, Melbourne, VIC, Australia.; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.; School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.; Translational Research Institute, Woolloongabba, QLD, Australia., Toh A; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.; School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.; Translational Research Institute, Woolloongabba, QLD, Australia., Hill P; Department of Pathology, University of Melbourne, Melbourne, VIC, Australia., Gilles C; Interdisciplinary Cluster for Applied Genoproteomics (GIGA)-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium., Waltham M; Invasion and Metastasis Unit, St. Vincent's Institute, Melbourne, VIC, Australia.; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.; School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia., Thompson EW; Invasion and Metastasis Unit, St. Vincent's Institute, Melbourne, VIC, Australia.; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.; School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.; Translational Research Institute, Woolloongabba, QLD, Australia.; Department of Surgery, University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia.
المصدر: Breast cancer research : BCR [Breast Cancer Res] 2017 Jul 27; Vol. 19 (1), pp. 86. Date of Electronic Publication: 2017 Jul 27.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 100927353 Publication Model: Electronic Cited Medium: Internet ISSN: 1465-542X (Electronic) Linking ISSN: 14655411 NLM ISO Abbreviation: Breast Cancer Res Subsets: MEDLINE
أسماء مطبوعة: Publication: London, UK : BioMed Central Ltd
Original Publication: London, UK : Current Science, c1999-
مواضيع طبية MeSH: Breast Neoplasms/*genetics , Cadherins/*genetics , Cell Proliferation/*genetics , Epithelial-Mesenchymal Transition/*genetics, Animals ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Epithelial Cells/pathology ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Mice ; Neoplasm Metastasis ; Xenograft Model Antitumor Assays
مستخلص: Background: Epithelial-to-mesenchymal transition (EMT) is associated with downregulated E-cadherin and frequently with decreased proliferation. Proliferation may be restored in secondary metastases by mesenchymal-to-epithelial transition (MET). We tested whether E-cadherin maintains epithelial proliferation in MDA-MB-468 breast cancer cells, facilitating metastatic colonization in severe combined immunodeficiency (SCID) mice.
Methods: EMT/MET markers were assessed in xenograft tumors by immunohistochemistry. Stable E-cadherin manipulation was effected by transfection and verified by Western blotting, immunocytochemistry, and quantitative polymerase chain reaction (qPCR). Effects of E-cadherin manipulation on proliferation and chemomigration were assessed in vitro by performing sulforhodamine B assays and Transwell assays, respectively. Invasion was assessed by Matrigel outgrowth; growth in vivo was assessed in SCID mice; and EMT status was assessed by qPCR. Hypoxic response of E-cadherin knockdown cell lines was assessed by qPCR after hypoxic culture. Repeated measures analysis of variance (ANOVA), one- and two-way ANOVA with posttests, and paired Student's t tests were performed to determine significance (p < 0.05).
Results: EMT occurred at the necrotic interface of MDA-MB-468 xenografts in regions of hypoxia. Extratumoral deposits (vascular and lymphatic inclusions, local and axillary nodes, and lung metastases) strongly expressed E-cadherin. MDA-MB-468 cells overexpressing E-cadherin were more proliferative and less migratory in vitro, whereas E-cadherin knockdown (short hairpin CDH1 [shCDH1]) cells were more migratory and invasive, less proliferative, and took longer to form tumors. shCDH1-MDA-MB-468 xenografts did not contain the hypoxia-induced necrotic areas observed in wild-type (WT) and shSCR-MDA-MB-468 tumors, but they did not exhibit an impaired hypoxic response in vitro. Although vimentin expression was not stimulated by E-cadherin knockdown in 2D or 3D cultures, xenografts of these cells were globally vimentin-positive rather than exhibiting regional EMT, and they expressed higher SNA1 than their in vitro counterparts. E-cadherin suppression caused a trend toward reduced lung metastasis, whereas E-cadherin overexpression resulted in the reverse trend, consistent with the increased proliferation rate and predominantly epithelial phenotype of MDA-MB-468 cells outside the primary xenograft. This was also originally observed in WT xenografts. Furthermore, we found that patients with breast cancer that expressed E-cadherin were more likely to have metastases.
Conclusions: E-cadherin expression promotes growth of primary breast tumors and conceivably the formation of metastases, supporting a role for MET in metastasis. E-cadherin needs to be reevaluated as a tumor suppressor.
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فهرسة مساهمة: Keywords: Breast cancer; E-cadherin; Epithelial-mesenchymal plasticity; Epithelial-to-mesenchymal transition; Metastasis; Proliferation
المشرفين على المادة: 0 (Cadherins)
تواريخ الأحداث: Date Created: 20170729 Date Completed: 20180427 Latest Revision: 20190115
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5530912
DOI: 10.1186/s13058-017-0880-z
PMID: 28750639
قاعدة البيانات: MEDLINE
الوصف
تدمد:1465-542X
DOI:10.1186/s13058-017-0880-z