Bakkalci Deniz, Al-Badri Georgina, Yang Wei, Nam Andy, Liang Yan, Khurram Syed Ali, Heavey Susan, Fedele Stefano, Cheema Umber
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.
Department of Mathematics, University College London, 25 Gordon Street, WC1H 0AY, London, UK.
Mater Today Bio. 2023 Dec 21;24:100923. doi: 10.1016/j.mtbio.2023.100923. eCollection 2024 Feb.
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.
基质细胞是肿瘤微环境（TME）的关键组成部分，将其整合到3D工程化肿瘤-基质模型中对于模拟肿瘤至关重要。通过构建具有不同肿瘤和基质区室的类肿瘤模型，已能够确定肿瘤细胞的基因表达如何因不同基质细胞的存在而发生改变和受到影响。成釉细胞瘤是颌骨的一种良性上皮性肿瘤。在工程化的多区室类肿瘤模型中，空间转录组学显示，在基质区室（骨基质）存在成骨细胞的情况下，成釉细胞瘤转录组中的癌基因上调。在构建牙龈成纤维细胞基质时，成釉细胞瘤肿瘤转录组显示基质重塑基因增加。这项研究提供了证据，表明基质对肿瘤行为具有特异性影响，并说明了为工程化肿瘤模型构建生物学相关基质的重要性。我们的新结果表明，工程化的成纤维细胞基质会导致成釉细胞瘤中基质重塑基因上调，这与模型中测得的侵袭直接相关。相比之下，骨基质的存在会增加成釉细胞瘤细胞中癌基因的表达。
