Implications of Three-Dimensional Cell Culture in Cancer Therapeutic Research

Poornima, Kolluri; Francis, Arul Prakash; Hoda, Muddasarul; Eladl, Mohamed Ahmed; Subramanian, S.; Veeraraghavan, Vishnu Priya; El‐Sherbiny, Mohamed; Asseri, Saad Mohamed; Hussamuldin, Abdulrahman Bashir Ahmed; Surapaneni, Krishna Mohan; Mony, Ullas; Rajagopalan, Rukkumani

doi:10.3389/fonc.2022.891673

Cited by 22 publications

(14 citation statements)

References 111 publications

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“…We cultured thymic tumors for further characterization. The organization of tumor cells in the three‐dimensional culture elucidates the pathobiological properties of the tumor, especially its microenvironment 13 . Therefore, we developed a standard two‐ and three‐dimensional cell culture.…”

Section: Resultsmentioning

confidence: 99%

“…The organization of tumor cells in the three‐dimensional culture elucidates the pathobiological properties of the tumor, especially its microenvironment. 13 Therefore, we developed a standard two‐ and three‐dimensional cell culture. Excised tumor cells were composed of two cell mixtures, namely, dish‐attached epithelial cells and floating lymphoid cells in standard 35 mm dishes (Figure 1e ).…”

Section: Resultsmentioning

confidence: 99%

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Experimental model of micronodular thymic neoplasm with lymphoid stroma

et al. 2022

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Background Micronodular thymic neoplasm with lymphoid stroma (MNT), a subtype of thymic tumor, is histopathologically characterized by micronodular thymic epithelial cell nests with lymphoid stroma. Despite the distinct histopathology of MNT, its pathogenesis remains unclear. Methods In this study, we aimed to examine a thymic tumor harboring thymic epithelial and lymphoid cells in a nonobese diabetic/severe combined immunodeficiency mouse. Results The excised tumor cells were cultured in vitro and comprised epithelial tumor cells and lymphoid cells. During a three‐dimensional cell culture, the epithelial tumor cells formed micronodular cell nests surrounded by lymphoid stroma. Notably, the lymphoid cells underwent apoptosis when they were separated from the epithelial tumor cells. Cutaneous transplantation of the cultured epithelial cells with splenocytes from BALB/c mice led to tumor formation, and these cells demonstrated a histopathology similar to that of human MNT in a nonobese diabetic/severe combined immunodeficiency mouse. Conclusion Given its overlapping features with human MNT, the transplanted tumor could serve as an experimental model of this disease.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Experimental model of micronodular thymic neoplasm with lymphoid stroma

et al. 2022

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“…Three-dimensional spheroids, which better mimic the physiological microenvironment of solid tumors, were shown to have a higher predictive value of therapy efficacy than standard 2D cultures [ 34 , 35 , 36 ], and are currently the preferred in vitro cancer model for drug testing. For this reason, we extended our therapy studies to 3D spheroid cultures of PanNET cells.…”

Section: Discussionmentioning

confidence: 99%

Combined Targeting of Pathogenetic Mechanisms in Pancreatic Neuroendocrine Tumors Elicits Synergistic Antitumor Effects

Gulde

Foscarini

April-Monn

et al. 2022

Cancers

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Pancreatic neuroendocrine neoplasms (PanNENs) are the second most common malignancy of the pancreas. Surgery remains the only curative treatment for localized disease. For patients with inoperable advanced or metastatic disease, few targeted therapies are available, but their efficacy is unpredictable and variable. Exploiting prior knowledge on pathogenetic processes involved in PanNEN tumorigenesis, we tested buparlisib (PI3K inhibitor) and ribociclib (CDK4/6 inhibitor), as single agents or in combination, in different preclinical models. First, we used cell lines representative of well-differentiated (INS-1E, NT-3) and poorly differentiated (BON-1) PanNENs. The combination of buparlisib with ribociclib reduced the proliferation of 2D and 3D spheroid cultures more potently than the individual drugs. Buparlisib, but not ribociclib, induced apoptosis. The anti-proliferative activity of the drugs correlated with downstream target inhibition at mRNA and protein levels. We then tested the drugs on primary islet microtissues from a genetic PanNET animal model (Men1-defective mice) and from wild-type mice: the drug combination was effective against the former without altering islet cell physiology. Finally, we treated PanNET patient-derived islet-like 3D tumoroids: the combination of buparlisib with ribociclib was effective in three out of four samples. Combined targeting of PI3K and CDK4/6 is a promising strategy for PanNENs spanning various molecular and histo-pathological features.

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“…Compared to 2D cultures and even to animal models, 3D cultures provide a more reliable tool in predicting how drug treatments will affect patients. [22] Most of the in vitro knowledge regarding spontaneous tumors in small animals comes from the study of 2D cell cultures or of the tumor itself. [1] However, it is well known that the monolayer 2D growth is represented by neoplastic cells having unlimited access to the ingredients of the medium, including oxygen, nutrients and signal molecules, which does not mimic a natural neoplastic mass.…”

Section: Immunophenotypic Comparison Between Primary Tumors and 3d Ce...mentioning

confidence: 99%

Morphologic, phenotypic, and genotypic similarities between primary tumors and corresponding 3D cultures grown in a repeatable system

Muscatello

Frabetti

Avallone

et al. 2023

Preprint

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Background: Three-dimensional (3D) cell cultures are the new frontier for reproducing the tumor micro-environment in vitro. The aims of the study were (1) to establish primary 3D cell cultures from canine spontaneous neoplasms and (2) to demonstrate the morphological, phenotypic and genetypic similarities between the primary canine neoplasms and the corresponding 3D cultures, through the expression of tumor differentiation markers. Results: Seven primary tumors were collected, including 4 carcinomas and 3 soft tissue sarcomas. 3D cell cultures reproduced the morphological features of the primary tumors and showed an overlapping immunophenotype of the primary epithelial tumors. Immunohistochemistry demonstrated the growth of stromal cells and macrophages admixed with the neoplastic epithelial component, reproducing the tumor microenvironment. Mesenchymal 3D cultures reproduced the immunophenotype of the primary tumor completely in 2 out of 3 examined cases while a discordant expression was documented for a single marker in one case. No single nucleotide variants or small indel were detected in TP53 or MDM2 genes, both in primary tumors and in 3D cell cultures specimens. In one sample, MDM2 amplicons were preferentially amplified compared to TP53 ones, indicating amplification of MDM2, detectable both in the primary tumor and in the corresponding cell culture specimen. Conclusion: Here we demonstrate a good cell morphology, phenotype and genetic profile overlap between primary tumors and the corresponding 3D cultures grown in a repeatable system.

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Implications of Three-Dimensional Cell Culture in Cancer Therapeutic Research

Cited by 22 publications

References 111 publications

Experimental model of micronodular thymic neoplasm with lymphoid stroma

Experimental model of micronodular thymic neoplasm with lymphoid stroma

Combined Targeting of Pathogenetic Mechanisms in Pancreatic Neuroendocrine Tumors Elicits Synergistic Antitumor Effects

Morphologic, phenotypic, and genotypic similarities between primary tumors and corresponding 3D cultures grown in a repeatable system

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