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Spatial transcriptomic interrogation of the tumour-stroma boundary in a 3D engineered model of ameloblastoma.
Bakkalci, Deniz; Al-Badri, Georgina; Yang, Wei; Nam, Andy; Liang, Yan; Khurram, Syed Ali; Heavey, Susan; Fedele, Stefano; Cheema, Umber.
Afiliação
  • Bakkalci D; UCL Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, Charles Bell House, 43-45 Foley Street, W1W 7TS, London, UK.
  • Al-Badri G; Department of Mathematics, University College London, 25 Gordon Street, WC1H 0AY, London, UK.
  • Yang W; NanoString Technologies, 530 Fairview Ave N, Seattle, WA 98109, USA.
  • Nam A; NanoString Technologies, 530 Fairview Ave N, Seattle, WA 98109, USA.
  • Liang Y; NanoString Technologies, 530 Fairview Ave N, Seattle, WA 98109, USA.
  • Khurram SA; Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, S10 2TA, Sheffield, UK.
  • Heavey S; UCL Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, Charles Bell House, 43-45 Foley Street, W1W 7TS, London, UK.
  • Fedele S; Eastman Dental Institute, University College London, London, UK.
  • Cheema U; UCL Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, Charles Bell House, 43-45 Foley Street, W1W 7TS, London, UK.
Mater Today Bio ; 24: 100923, 2024 Feb.
Article em En | MEDLINE | ID: mdl-38226014
ABSTRACT
Stromal cells are key components of the tumour microenvironment (TME) and their incorporation into 3D engineered tumour-stroma models is essential for tumour mimicry. By engineering tumouroids with distinct tumour and stromal compartments, it has been possible to identify how gene expression of tumour cells is altered and influenced by the presence of different stromal cells. Ameloblastoma is a benign epithelial tumour of the jawbone. In engineered, multi-compartment tumouroids spatial transcriptomics revealed an upregulation of oncogenes in the ameloblastoma transcriptome where osteoblasts were present in the stromal compartment (bone stroma). Where a gingival fibroblast stroma was engineered, the ameloblastoma tumour transcriptome revealed increased matrix remodelling genes. This study provides evidence to show the stromal-specific effect on tumour behaviour and illustrates the importance of engineering biologically relevant stroma for engineered tumour models. Our novel results show that an engineered fibroblast stroma causes the upregulation of matrix remodelling genes in ameloblastoma which directly correlates to measured invasion in the model. In contrast the presence of a bone stroma increases the expression of oncogenes by ameloblastoma cells.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article