2022
DOI: 10.3389/fonc.2022.881207
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Development of a Multicellular 3D Tumor Model to Study Cellular Heterogeneity and Plasticity in NSCLC Tumor Microenvironment

Abstract: Heterogeneity is a characteristic feature of solid tumors. Intra-tumor heterogeneity includes phenotypic diversity, epigenetic abnormalities, cell proliferation, and plasticity that eventually drives disease progression. Studying tumor heterogeneity in 2D culture is challenging as it cannot simulate the microenvironmental features, such as hypoxia, nutrient unavailability, and cell-ECM interactions. We propose the development of multicellular (tri-culture) 3D spheroids using a hanging drop method to study the … Show more

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Cited by 10 publications
(2 citation statements)
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“…For example, Ni, Makino, and Tabata conducted experiments with CAFs and their migratory influence on small-cell lung cancer cells [ 35 ]. Another study on non-small-cell lung cancer underlines the influence of TME in an in vitro tumor multicellular spheroid model on normal lung fibroblast and monocyte cell lines, which differentiated into CAF and tumor-associated macrophages (TAM), respectively [ 36 ]. Work by Alzeeb et al exemplifies the use of primary CAFs and their varying influences on two human gastric cancer cell lines co-cultured in a direct 3D model [ 37 ].…”
Section: Discussionmentioning
confidence: 99%
“…For example, Ni, Makino, and Tabata conducted experiments with CAFs and their migratory influence on small-cell lung cancer cells [ 35 ]. Another study on non-small-cell lung cancer underlines the influence of TME in an in vitro tumor multicellular spheroid model on normal lung fibroblast and monocyte cell lines, which differentiated into CAF and tumor-associated macrophages (TAM), respectively [ 36 ]. Work by Alzeeb et al exemplifies the use of primary CAFs and their varying influences on two human gastric cancer cell lines co-cultured in a direct 3D model [ 37 ].…”
Section: Discussionmentioning
confidence: 99%
“…Cell-extrinsic factors like TME consisting of the immune system as well as tumor cells and the cancer-associated extracellular matrix (ECM) that contain numerous receptors that have been strongly linked to providing a niche for CSCs are also required for the development of plasticity. We will not be focussing on the role of the microenvironment in cancer cell plasticity, which is an area of intense research [5,6] with some excellent review articles on this subject [7][8][9]. The importance of cancer cell plasticity becomes even more relevant in the context of therapeutic intervention in the disease.…”
Section: Introductionmentioning
confidence: 99%