التفاصيل البيبلوغرافية
| العنوان: |
Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation |
| المؤلفون: |
Vinci, Maria, Gowan, Sharon, Boxall, Frances, Patterson, Lisa, Zimmermann, Miriam, Court, William, Lomas, Cara, Mendiola, Marta, Hardisson, David, Eccles, Suzanne A |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2012 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
3D, angiogenesis, drug response, high throughput, invasion, migration, tumor spheroids |
| الوصف: |
Background There is overwhelming evidence that in vitro three-dimensional tumor cell cultures more accurately reflect the complex in vivo microenvironment than simple two-dimensional cell monolayers, not least with respect to gene expression profiles, signaling pathway activity and drug sensitivity. However, most currently available three-dimensional techniques are time consuming and/or lack reproducibility; thus standardized and rapid protocols are urgently needed. Results To address this requirement, we have developed a versatile toolkit of reproducible three-dimensional tumor spheroid models for dynamic, automated, quantitative imaging and analysis that are compatible with routine high-throughput preclinical studies. Not only do these microplate methods measure three-dimensional tumor growth, but they have also been significantly enhanced to facilitate a range of functional assays exemplifying additional key hallmarks of cancer, namely cell motility and matrix invasion. Moreover, mutual tissue invasion and angiogenesis is accommodated by coculturing tumor spheroids with murine embryoid bodies within which angiogenic differentiation occurs. Highly malignant human tumor cells were selected to exemplify therapeutic effects of three specific molecularly-targeted agents: PI-103 (phosphatidylinositol-3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor), 17- N -allylamino-17-demethoxygeldanamycin (17-AAG) (heat shock protein 90 (HSP90) inhibitor) and CCT130234 (in-house phospholipase C (PLC)γ inhibitor). Fully automated analysis using a Celigo cytometer was validated for tumor spheroid growth and invasion against standard image analysis techniques, with excellent reproducibility and significantly increased throughput. In addition, we discovered key differential sensitivities to targeted agents between two-dimensional and three-dimensional cultures, and also demonstrated enhanced potency of some agents against cell migration/invasion compared with proliferation, suggesting their preferential ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
http://www.biomedcentral.com/1741-7007/10/29Test |
| الإتاحة: |
http://www.biomedcentral.com/1741-7007/10/29Test |
| حقوق: |
Copyright 2012 Vinci et al; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.D53530C1 |
| قاعدة البيانات: |
BASE |
