Development of tissue-engineered models of oral dysplasia and early invasive oral squamous cell carcinoma

Colley, Helen; Hearnden, Vanessa; Jones, Aled; Weinreb, Paul H.; Violette, Shelia M.; MacNeil, Sheila; Thornhill, Martin H.; Murdoch, Craig

doi:10.1038/bjc.2011.403

Cited by 87 publications

(88 citation statements)

References 47 publications

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“…The solution was then left for 7 days under continuous stirring at room temperature before sonication (15 min) and purification via gel permeation chromatography. Polymersome size was determined by dynamic light scattering and encapsulated drug concentrations determined by high performance liquid chromatography ( Table 1) Normal oral keratinocytes (NOK) and fibroblasts (NOF) were isolated from biopsies obtained from the buccal and gingival oral mucosa from patients during routine dental procedures with written, informed consent (ethical approval number 09/H1308/66) as previously described 29 .…”

Section: Preparation and Characterisation Of Chemotherapeutic Loaded mentioning

confidence: 99%

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

et al. 2014

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Polymersomes have the potential to encapsulate and deliver chemotherapeutic drugs into tumour cells, reducing off-target toxicity that often compromises anti-cancer treatment. Here we assess the ability of the pH-sensitive poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC)-poly 2-(diisopropylamino)ethyl methacrylate (PDPA) polymersomes to encapsulate chemotherapeutic agents for effective combinational anti-cancer therapy. Polymersome uptake and ability to deliver encapsulated drugs into healthy normal oral cells and oral head and neck squamous cell carcinoma (HNSCC) cells was measured in two and three-dimensional culture systems. PMPC-PDPA polymersomes were more rapidly internalised by HNSCC cells compared to normal oral cells. Polymersome cellular up-take was found to be mediated by class B scavenger receptors.We also observed that these receptors are more highly expressed by cancer cells compared to normal oral cells, enabling polymersome-mediated targeting. Doxorubicin and paclitaxel were encapsulated into pH-sensitive PMPC-PDPA polymersomes with high efficiencies either in isolation or as a dual-load for both singular and combinational delivery. In monolayer culture, only a short exposure to drug-loaded polymersomes was required to elicit a strong cytotoxic effect. When delivered to three-dimensional tumour models, PMPC-PDPA polymersomes were able to penetrate deep into the centre of the spheroid resulting in extensive cell damage when loaded with both singular and dual-loaded chemotherapeutics. PMPC-PDPA polymersomes offer a novel system for the effective delivery of chemotherapeutics for the treatment of HNSCC.Moreover, the preferential internalisation of PMPC polymersomes by exploiting elevated scavenger receptor expression on cancer cells opens up the opportunity to target polymersomes to tumours.3

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Section: Preparation and Characterisation Of Chemotherapeutic Loaded mentioning

confidence: 99%

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

et al. 2014

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“…In previous studies, the SCC4 spheroids were cultured only up to 72 h [4]. Therefore, the aim of this study was to compare three different culture methods to create a long-term culture model of threedimensional spheroids of the tongue cancer cell line SCC4.…”

Section: Objectivementioning

confidence: 99%

“…Stage III is defined as when the tumour 1 These authors contributed equally to this work. can be seen in the lymph nodes and stage IV when the tumour is metastatic throughout the body [3,4]. The 5-year survival rates for patients who present with stage III or IV are between 10% and 40% [5,6].…”

Section: Introductionmentioning

confidence: 99%

Long-term 3D culture of the SCC4 cell line using three different culture methods and initial seeding densities

Rustamov

Rudolf

Yagublu

et al. 2017

JCB

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Abstract. INTRODUCTION:In recent years, many different methods were introduced for generation of 3D cell culture. However, many currently available three-dimensional techniques are not suitable for certain cell lines and sometimes showed a lack of reproducibility. Therefore, specific protocols for cell lines are needed. In this work, we demonstrate different methods of generating 3D cell culture for SCC4 tongue cancer cell line and discuss their applicability. MATERIALS AND METHODS:Using three different methods, tumor spheroids were generated from SCC4 cells and cultured for 20 days. To investigate the influence of initial seeding density on spheroid morphology and size during long term culture, the same set of different cell numbers was used for each method. Using phase-contrast microscopy, spheroids were monitored until day 20 and their sizes were determined. RESULTS: We observed that spheroids were formed within 24 hours regardless of the method and initial cell density. Further, in all groups the spheroid size was maximal at day 2, followed by a decline until day 20. Spheroids remained stable until day 20 independent of initial seeding concentration in all groups. DISCUSSION: We have generated long-term culture spheroids of SCC4 cells. The size of the spheroids can be influenced by varying the initial cell seeding density until day 20. This may be useful if different sizes of spheroids are required, e.g. in hypoxia research.

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“…When cultured in 3D, the D20 cells produce an epithelium that resembles a severe oral dysplasia (often a pre-cursor to oral cancer), while the SCC9 and Cal27 cell lines produce models resembling squamous cell carcinoma and become invasive when cultured longer. 26 The main finding of this study was that where there were gross disruptions to the epithelia of skin and oral models by the presence of cancer cells these were visible in the OCT images. These disruptions were comparable to disruptions seen with histological examination of tissue sections obtained from these samples.…”

Section: Discussionmentioning

confidence: 76%

Evaluating the use of optical coherence tomography for the detection of epithelial cancers in vitro

Smith

Hearnden

et al. 2011

J. Biomed. Opt.

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Abstract. Optical coherence tomography (OCT) is a noninvasive imaging methodology that is able to image tissue to depths of over 1 mm. Many epithelial conditions, such as melanoma and oral cancers, require an invasive biopsy for diagnosis. A noninvasive, real-time, point of care method of imaging depth-resolved epithelial structure could greatly improve early diagnosis and long-term monitoring in patients. Here, we have used tissue-engineered (TE) models of normal skin and oral mucosa to generate models of melanoma and oral cancer. We have used these to determine the ability of OCT to image epithelial differences in vitro. We report that while in vivo OCT gives reasonable depth information for both skin and oral mucosa, in vitro the information provided is less detailed but still useful. OCT can provide reassurance on the development of TE models of skin and oral mucosa as they develop in vitro. OCT was able to detect the gross alteration in the epithelium of skin and mucosal models generated with malignant cell lines but was less able to detect alteration in the epithelium of TE models that mimicked oral dysplasia or, in models where tumor cells had penetrated into the dermis. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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Development of tissue-engineered models of oral dysplasia and early invasive oral squamous cell carcinoma

Cited by 87 publications

References 47 publications

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

Long-term 3D culture of the SCC4 cell line using three different culture methods and initial seeding densities

Evaluating the use of optical coherence tomography for the detection of epithelial cancers in vitro

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