دورية أكاديمية
Generation and characterisation of two D2A1 mammary cancer sublines to model spontaneous and experimental metastasis in a syngeneic BALB/c host.
العنوان: | Generation and characterisation of two D2A1 mammary cancer sublines to model spontaneous and experimental metastasis in a syngeneic BALB/c host. |
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المؤلفون: | Jungwirth U; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK ute.jungwirth@icr.ac.uk clare.isacke@icr.ac.uk., van Weverwijk A; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK., Melake MJ; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK.; German Cancer Research Center, DKFZ, 69120, Heidelberg, Germany., Chambers AF; Department of Oncology, University of Western Ontario, London, Ontario, N6A 4L6, Canada., Gao Q; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK., Fivaz M; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK., Isacke CM; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK ute.jungwirth@icr.ac.uk clare.isacke@icr.ac.uk. |
المصدر: | Disease models & mechanisms [Dis Model Mech] 2018 Jan 18; Vol. 11 (1). Date of Electronic Publication: 2018 Jan 18. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Company of Biologists Ltd Country of Publication: England NLM ID: 101483332 Publication Model: Electronic Cited Medium: Internet ISSN: 1754-8411 (Electronic) Linking ISSN: 17548403 NLM ISO Abbreviation: Dis Model Mech Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Cambridge : Company of Biologists Ltd., c2008- |
مواضيع طبية MeSH: | Mammary Neoplasms, Animal/*pathology, Animals ; Cell Adhesion ; Cell Line, Tumor ; Databases, Genetic ; Disease Models, Animal ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Immunocompromised Host ; Mammary Neoplasms, Animal/genetics ; Mice, Inbred BALB C ; Neoplasm Metastasis ; Stromal Cells/metabolism ; Stromal Cells/pathology |
مستخلص: | Studying the complex mechanisms underlying breast cancer metastasis and therapy response necessitates relevant in vivo models, particularly syngeneic models with an intact immune system. Two syngeneic spontaneously metastatic sublines, D2A1-m1 and D2A1-m2, were generated from the poorly metastasising BALB/c-derived D2A1 cell line by serial in vivo passaging. In vivo and in vitro analyses revealed distinct and shared characteristics of the metastatic D2A1-m1 and D2A1-m2 sublines. In particular, D2A1-m1 cells are more aggressive in experimental metastasis assays, while D2A1-m2 cells are more efficient at disseminating from the primary tumour in spontaneous metastasis assays. Surprisingly, classical metastasis-associated in vitro phenotypes, such as enhanced proliferation, migration and invasion, are reduced in the sublines compared to the parental cell line. Further, evasion of immune control cannot fully explain their enhanced metastatic properties. By contrast, both sublines show increased resistance to apoptosis when cultured in non-adherent conditions and, for the D2A1-m2 subline, increased 3D tumour spheroid growth. Moreover, the enhanced spontaneous metastatic phenotype of the D2A1-m2 subline is associated with an increased ability to recruit an activated tumour stroma. The metastatic D2A1-m1 and D2A1-m2 cell lines provide additional syngeneic models for investigating the different steps of the metastatic cascade and thereby represent valuable tools for breast cancer researchers. Finally, this study highlights that morphology and cell behaviour in 2D cell-based assays cannot be used as a reliable predictor of metastatic behaviour in vivo . Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2018. Published by The Company of Biologists Ltd.) |
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معلومات مُعتمدة: | 15-0355 United Kingdom AICR_ Worldwide Cancer Research |
فهرسة مساهمة: | Keywords: BALB/c; D2A1; Mammary cancer; Metastatic sublines; Spontaneous metastasis; Syngeneic |
تواريخ الأحداث: | Date Created: 20171207 Date Completed: 20181011 Latest Revision: 20210109 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC5818081 |
DOI: | 10.1242/dmm.031740 |
PMID: | 29208627 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1754-8411 |
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DOI: | 10.1242/dmm.031740 |