Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer

Hagemann, Jan; Jacobi, Christian; Hahn, Moritz; Schmid, Vanessa; Welz, Christian; Schwenk‐Zieger, Sabina; Stauber, Roland H.; Baumeister, Philipp; Becker, Sven

doi:10.21873/anticanres.11555

Cited by 65 publications

(70 citation statements)

References 64 publications

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“…This is comparable to the results presented by Adcock et al, where CAL-27 MCS grew to 50-100 µm in diameter within 3 to 4 days (2). Hagemann et al also showed similar results by generating CAL-27 MCS that reached a diameter of 1-3 mm within 5 days (12).…”

Section: Discussionmentioning

confidence: 61%

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Generation of highly differentiated BHY oral squamous cell carcinoma multicellular spheroids

et al. 2017

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Abstract. Three-dimensional (3D) multicellular spheroids (MCS) are considered suitable models in cancer research and anticancer drug development. Although studying the complex tumour characteristics from all different degrees of malignancy is vital, MCS generation has only been described in a few moderately-and poorly differentiated oral squamous cell carcinoma (OSCC) cell lines. No previous study has demonstrated the MCS formation in a highly differentiated OSCC cell line. For the first time, the present study aimed to generate MCS from the highly differentiated OSCC cell line BHY. BHY spheroids were grown in three independent experiments in 96-well plates through the use of the liquid overlay technique. Although BHY cells are grow slowly and are difficult to culture, they formed compact MCS within 24 h. After 3 days of incubation, no further increase in spheroid size was observed. MCS were harvested, paraffin-embedded and 2 µm tissue sections were prepared for further analysis. The diameter and volume of each spheroid were determined. BHY MCS diameter ranged between 46.76 and 233.26 µm, with a volume range from 5.35x10 4 -6.65x10 6 µm³. In conclusion, using the liquid overlay technique, the highly differentiated OSCC cell line BHY forms different sized spheroids, which may be used for further investigations.

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Section: Discussionmentioning

confidence: 61%

“…The advantage of the used method lies in its easy practicability compared to other protocols described in the literature that use the Matrigel, Hanging Drops, or doing Ultra-Low Attachment Assays (2,11,12).…”

Section: Discussionmentioning

confidence: 99%

Generation of highly differentiated BHY oral squamous cell carcinoma multicellular spheroids

et al. 2017

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“…Indeed, a minimal amount of tumor cells are required to form spheroids 63,64 , and cutaneous cells can easily be obtained from a small biopsy to produce skin. Spheroids and organoids are already tested as tools to optimize treatment for each patient, but the role of TME is not recapitulated in these models.…”

Section: Discussionmentioning

confidence: 99%

Tissue-engineered 3D melanoma model with blood and lymphatic capillaries for drug development

Bourland

Fradette

Auger

2018

Sci Rep

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While being the rarest skin cancer, melanoma is also the deadliest. To further drug discovery and improve clinical translation, new human cell-based in vitro models are needed. Our work strives to mimic the melanoma microenvironment in vitro as an alternative to animal testing. We used the self-assembly method to produce a 3D human melanoma model exempt of exogenous biomaterial. This model is based on primary human skin cells and melanoma cell lines while including a key feature for tumor progression: blood and lymphatic capillaries. Major components of the tumor microenvironment such as capillaries, human extracellular matrix, a stratified epidermis (involucrin, filaggrin) and basement membrane (laminin 332) are recapitulated in vitro. We demonstrate the persistence of CD31+ blood and podoplanin+/LYVE-1+ lymphatic capillaries in the engineered tissue. Chronic treatment with vemurafenib was applied to the model and elicited a dose-dependent response on proliferation and apoptosis, making it a promising tool to test new compounds in a human-like environment.

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“…Hagemann et al. studied formation of spheroids from the PiCa cell line, which was generated from primary carcinoma specimens without enzymatic digestions of single cells . Spheroids were grown using two methods—1) the method of hanging droplet, where cell aggregation is promoted by gravitational accumulation of cells in the water–air interface of droplets; and 2) ultra‐low attachment plates (ULA), where cells are prevented from attaching to the surface, which leads to cell aggregation.…”

Section: Dsrt On 3d Cell Culture Modelsmentioning

confidence: 99%

“…Spheroids were grown using two methods—1) the method of hanging droplet, where cell aggregation is promoted by gravitational accumulation of cells in the water–air interface of droplets; and 2) ultra‐low attachment plates (ULA), where cells are prevented from attaching to the surface, which leads to cell aggregation. The authors successfully formed spheroids using both methods and demonstrated reduction of spheroid diameter by treating them with cisplatin, 5‐fluorouracil (5‐FU), or radiation …”

Section: Dsrt On 3d Cell Culture Modelsmentioning

confidence: 99%

Precision Medicine in Oncology: In Vitro Drug Sensitivity and Resistance Test (DSRT) for Selection of Personalized Anticancer Therapy

Popova

Levkin

2020

Advanced Therapeutics

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Precision or personalized medicine aims to determine an optimal therapy for each individual patient. In oncology techniques such as next generation sequencing, mRNA‐sequencing, ChIP‐sequencing, and mass spectrometry are used to perform a full molecular profiling for each patient. However, it is not always possible to determine a suitable treatment for an individual cancer based on molecular profiling, mostly due to the high level of tumor heterogeneity. In vitro drug sensitivity and resistance test (DSRT) can be performed on cancer cells or tissues obtained from a patient with a panel of anticancer compounds in order to experimentally define sensitivity and resistance of each individual cancer. In combination with molecular profiling, DSRT can provide a fuller picture about the nature of disease, allowing for finding more appropriate therapy for each individual patient. In this progress report, studies describing in vitro DSRTs on 2D and 3D cell models based on patient‐derived cells are reviewed and challenges and future steps needed for the adaptation of these systems in clinics are discussed.

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Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer

Cited by 65 publications

References 64 publications

Generation of highly differentiated BHY oral squamous cell carcinoma multicellular spheroids

Generation of highly differentiated BHY oral squamous cell carcinoma multicellular spheroids

Tissue-engineered 3D melanoma model with blood and lymphatic capillaries for drug development

Precision Medicine in Oncology: In Vitro Drug Sensitivity and Resistance Test (DSRT) for Selection of Personalized Anticancer Therapy

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