In vitro models for head and neck cancer: Current status and future perspective

Moya-Garcia, Christian R.; Okuyama, Hideaki; Sadeghi, N.; Li, Jianyu; Tabrizian, Maryam; Li‐Jessen, Nicole Y. K.

doi:10.3389/fonc.2022.960340

Cited by 13 publications

(24 citation statements)

References 177 publications

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“…Well defined in vitro models can partially substitute the use of animals in some circumstances. Three-dimensional culture models, including spheroids, a 3D organotypic co-culture (3D-OTC) model, and a 3D collagen-based scaffold model, represent valuable research resources in this field [ 42 , 43 , 44 ]. In our study, we used a tumor sphere formation assay to identify stem-like characteristics of CSC in the head and neck ( Figure 4 E–J).…”

Section: Discussionmentioning

confidence: 99%

SHMT2 Induces Stemness and Progression of Head and Neck Cancer

Jin

Jung

Lim

et al. 2022

IJMS

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Various enzymes in the one-carbon metabolic pathway are closely related to the development of tumors, and they can all be potential targets for cancer therapy. Serine hydroxymethyltransferase2 (SHMT2), a key metabolic enzyme, is very important for the proliferation and growth of cancer cells. However, the function and mechanism of SHMT2 in head and neck cancer (HNC) are not clear. An analysis of The Cancer Genome Atlas (TCGA) data showed that the expression of SHMT2 was higher in tumor tissue than in normal tissue, and its expression was significantly associated with male sex, aggressive histological grade, lymph node metastasis, distant metastasis, advanced TNM stage, and lymphovascular invasion in HNC. SHMT2 knockdown in FADU and SNU1041 cell lines significantly inhibited cell proliferation, colony formation, migration, and invasion. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using TCGA data revealed that SHMT2 was closely related to cancer stem cell regulation and maintenance. Furthermore, we found that silencing SHMT2 inhibited the expression of stemness markers and tumor spheroid formation compared with a control group. On the contrary, stemness markers were significantly increased after SHMT2 overexpression in HEP-2 cells. Interestingly, we found that knocking down SHMT2 reduced the expression of genes related to the Notch and Wnt pathways. Finally, silencing SHMT2 significantly reduced tumor growth and decreased stemness markers in a xenograft model. Taken together, our study suggests that targeting SHMT2 may play an important role in inhibiting HNC progression.

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Section: Discussionmentioning

confidence: 99%

SHMT2 Induces Stemness and Progression of Head and Neck Cancer

Jin

Jung

Lim

et al. 2022

IJMS

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“…A liquid biopsy approach allows for a non-invasive and accessible screening method for HNC and it can also provide sample repeatability and real-time monitoring at an inexpensive cost [95,103]. In screening for HNC, the most common analytes used from liquid biopsies are CTCs, ctDNAs, EVs, mRNA, and miRNAs [23,104]. Existing technologies used to quantitively evaluate these analytes from liquid biopsies range from flow cytometry, mass-spectrometry, real-time PCR (qRT-PCR), or size-exclusion chromatography (SEC) depending on the analyte [19].…”

Section: Microfluidic Systems For Hnc Diagnosis and Screeningmentioning

confidence: 99%

“…Additionally, the ability to regularly monitor multiple key biomarkers in parallel or screen in real-time HNC in numerous patients remains a challenge. Another major limitation of existing screening and detection techniques includes the specificity and sensitivity to detect and isolate low levels of analyte concentrations [19,23,105]. Table 2 illustrates the studies that have employed microfluidic methods utilizing liquid biopsy samples for early detection and screening of head HNCs.…”

Section: Microfluidic Systems For Hnc Diagnosis and Screeningmentioning

confidence: 99%

“…Bioengineered tumor spheroids and organotypic models have played a pivotal role in our understanding of TME and serve as versatile tools in modeling multicellular microtissues in tunable matrices. Over the last five years, approximately 74% of research studies in the field of HNCs have predominantly concentrated on utilizing spheroid-, scaffold-, and organoid-based cultures for 3D modeling [23]. Indeed, these complex spheroid models have added a wealth of information to our understanding of TME and the differential drug sensitivity between 2D monolayer and 3D cultures, including xenograft models [24,25].…”

Section: Introductionmentioning

confidence: 99%

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Mapping the Potential of Microfluidics in Early Diagnosis and Personalized Treatment of Head and Neck Cancers

Pillai,

Kwan,

Yaziji

et al. 2023

Cancers

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Head and neck cancers (HNCs) account for ~4% of all cancers in North America and encompass cancers affecting the oral cavity, pharynx, larynx, sinuses, nasal cavity, and salivary glands. The anatomical complexity of the head and neck region, characterized by highly perfused and innervated structures, presents challenges in the early diagnosis and treatment of these cancers. The utilization of sub-microliter volumes and the unique phenomenon associated with microscale fluid dynamics have facilitated the development of microfluidic platforms for studying complex biological systems. The advent of on-chip microfluidics has significantly impacted the diagnosis and treatment strategies of HNC. Sensor-based microfluidics and point-of-care devices have improved the detection and monitoring of cancer biomarkers using biological specimens like saliva, urine, blood, and serum. Additionally, tumor-on-a-chip platforms have allowed the creation of patient-specific cancer models on a chip, enabling the development of personalized treatments through high-throughput screening of drugs. In this review, we first focus on how microfluidics enable the development of an enhanced, functional drug screening process for targeted treatment in HNCs. We then discuss current advances in microfluidic platforms for biomarker sensing and early detection, followed by on-chip modeling of HNC to evaluate treatment response. Finally, we address the practical challenges that hinder the clinical translation of these microfluidic advances.

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“…Analyzing stroma-tumor interactions in 3D systems is currently of growing interest to reproduce tumor mass architecture [ 17 ]. Using a hybrid 3D culture model offers a unique investigation to assess tumor transition, noting the heterogeneous cellularity of the TME [ 18 ]. In our study, we analyzed the effect of TME, EMT, and tumor–stroma interaction in a model of 3D stroma-tumor spheroids (STSs) using MSCs and the established tumor cell line SCC-040.…”

Section: Introductionmentioning

confidence: 99%

EMT and Tumor Turning Point Analysis in 3D Spheroid Culture of HNSCC and Mesenchymal Stem Cells

Brylka

Böhrnsen

2022

Biomedicines

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The prognosis, metastasis, and behavior of head and neck squamous cancer cells are influenced by numerous factors concerning the tumor microenvironment, intercellular communication, and epithelial-to-mesenchymal transition (EMT). The aim of this study was to examine the codependent interaction of the mesenchymal stroma with head and neck squamous cell carcinoma (HNSCC) in a 3D spheroid structure. To simulate stroma-rich and -poor 3D tumor microenvironments, cells of the established cell SCC-040 were cultured with human mesenchymal stromal cells (MSCs), forming 3D stroma-tumor spheroids (STSs). STSs were compared to uniform spheroids of SCC-040 and MSC, respectively. The expressions of CD24, β-catenin, SNAI2, and ZEB2 were analyzed via RT-qPCR. The immunohistochemical expressions of E-cadherin, connexin 43, vimentin, and emmprin were analyzed, and protein expression pathways as well as Akt signaling were assessed via protein analysis. A promotive effect on the expressions of EMT markers ZEB2 (p = 0.0099), SNAI2 (p = 0.0352), and β-catenin (p = 0.0031) was demonstrated in STSs, as was the expression of Akt pathway proteins mTOR (p = 0.007), Erk1/2 (p = 0.0045), and p70 S6 Kinase (p = 0.0016). Our study demonstrated a change in genetic expression patterns early on in tumor development, indicating a tumor turning point.

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In vitro models for head and neck cancer: Current status and future perspective

Cited by 13 publications

References 177 publications

SHMT2 Induces Stemness and Progression of Head and Neck Cancer

SHMT2 Induces Stemness and Progression of Head and Neck Cancer

Mapping the Potential of Microfluidics in Early Diagnosis and Personalized Treatment of Head and Neck Cancers

EMT and Tumor Turning Point Analysis in 3D Spheroid Culture of HNSCC and Mesenchymal Stem Cells

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