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Modelling stromal compartments to recapitulate the ameloblastoma tumour microenvironment

Zubir Amir Zaki Abdullah; Cheema Umber; Khurram Syed Ali; Pape Judith; Bakkalci Deniz; Heikinheimo Kristiina; Fedele Stefano

Modelling stromal compartments to recapitulate the ameloblastoma tumour microenvironment

Zubir Amir Zaki Abdullah
Cheema Umber
Khurram Syed Ali
Pape Judith
Bakkalci Deniz
Heikinheimo Kristiina
Fedele Stefano
Katso/Avaa
1-s2.0-S2590028522000254-main.pdf (4.123Mb)
Lataukset: 

Elsevier
doi:10.1016/j.mbplus.2022.100125
URI
https://doi.org/10.1016/j.mbplus.2022.100125
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe202301132731
Tiivistelmä
Tumour development and progression is dependent upon tumour cell interaction with the tissue stroma. Bioengineering the tumour-stroma microenvironment (TME) into 3D biomimetic models is crucial to gain insight into tumour cell development and progression pathways and identify therapeutic targets. Ameloblastoma is a benign but locally aggressive epithelial odontogenic neoplasm that mainly occurs in the jawbone and can cause significant morbidity and sometimes death. The molecular mechanisms for ameloblastoma progression are poorly understood. A spatial model recapitulating the tumour and stroma was engineered to show that without a relevant stromal population, tumour invasion is quantitatively decreased. Where a relevant stroma was engineered in dense collagen populated by gingival fibroblasts, enhanced receptor activator of nuclear factor kappa-B ligand (RANKL) expression was observed and histopathological properties, including ameloblastoma tumour islands, developed and were quantified. Using human osteoblasts (bone stroma) further enhanced the biomimicry of ameloblastoma histopathological phenotypes. This work demonstrates the importance of the two key stromal populations, osteoblasts, and gingival fibroblasts, for accurate 3D biomimetic ameloblastoma modelling.
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