scholarly journals A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing

2019 ◽  
Vol 20 (14) ◽  
pp. 3428 ◽  
Author(s):  
Sakinah Hassan ◽  
Karin J. Purdie ◽  
Jun Wang ◽  
Catherine A. Harwood ◽  
Charlotte M. Proby ◽  
...  

Background: Cutaneous squamous cell carcinoma (cSCC) incidence continues to rise with increasing morbidity and mortality, with limited treatment options for advanced disease. Future improvements in targeted therapy will rely on advances in genomic/transcriptomic understanding and the use of model systems for basic research. We describe here the panel of 16 primary and metastatic cSCC cell lines developed and characterised over the past three decades in our laboratory in order to provide such a resource for future preclinical research and drug screening. Methods: Primary keratinocytes were isolated from cSCC tumours and metastases, and cell lines were established. These were characterised using short tandem repeat (STR) profiling and genotyped by whole exome sequencing. Multiple in vitro assays were performed to document their morphology, growth characteristics, migration and invasion characteristics, and in vivo xenograft growth. Results: STR profiles of the cSCC lines allow the confirmation of their unique identity. Phylogenetic trees derived from exome sequence analysis of the matched primary and metastatic lines provide insight into the genetic basis of disease progression. The results of in vivo and in vitro analyses allow researchers to select suitable cell lines for specific experimentation. Conclusions: There are few well-characterised cSCC lines available for widespread preclinical experimentation and drug screening. The described cSCC cell line panel provides a critical tool for in vitro and in vivo experimentation.

2014 ◽  
Vol 306 (5) ◽  
pp. 489-496 ◽  
Author(s):  
Dae-Kyoung Choi ◽  
Zheng Jun Li ◽  
In-Kyu Chang ◽  
Min-Kyung Yeo ◽  
Jin-Man Kim ◽  
...  

2015 ◽  
Vol 10 (4) ◽  
pp. 501-508 ◽  
Author(s):  
Natalie R. Young ◽  
Christian Soneru ◽  
Jing Liu ◽  
Tatyana A. Grushko ◽  
Ashley Hardeman ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Long Li ◽  
Hai-Chao Liu ◽  
Cheng Wang ◽  
Xiqiang Liu ◽  
Feng-Chun Hu ◽  
...  

Abnormal expression ofβ-catenin contributes to tumor development, progression, and metastasis in various cancers. However, little is known about the relationship between abnormal expression ofβ-catenin and cisplatin chemotherapy in oral squamous cell carcinoma (OSCC). The present study aimed to investigate the effect ofβ-catenin on OSCC cisplatin resistance and evaluated the drug susceptibility of stable cell lines withβ-catenin knockin and knockdown. In this study, we found that higher expression level ofβ-catenin can be observed in CDDP-treated cell lines as compared with the control group. Furthermore, the expression levels ofβ-catenin increased in both a concentration- and time-dependent manner with the cisplatin treatment. More importantly, the nuclear translocation ofβ-catenin could also be observed by confocal microscope analysis. Stable cell lines with CTNNB1 knockin and knockdown were established to further investigate the potential role and mechanism ofβ-catenin in the chemoresistance of OSCC in vitro and in vivo. Our findings indicated that overexpression ofβ-catenin promoted cisplatin resistance in OSCC in vitro and in vivo. We confirmed that GSK-3β, C-myc, Bcl-2, P-gp, and MRP-1 were involved inβ-catenin-mediated drug resistance. Our findings indicate that the Wnt/β-catenin signaling pathway may play important roles in cisplatin resistance in OSCC.


2021 ◽  
Vol 10 (5) ◽  
pp. 2219-2228
Author(s):  
Lipeng Gao ◽  
Tim Hua Wang ◽  
Champ Peng Chen ◽  
Jan Jian Xiang ◽  
Xu-Bo Zhao ◽  
...  

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Erliang Guo ◽  
Xionghui Mao ◽  
Xueying Wang ◽  
Lunhua Guo ◽  
Changming An ◽  
...  

AbstractHead and neck squamous cell carcinoma (HNSCC) is a common cancer with high mortality. Anilin actin-binding protein (ANLN) has been reported to be associated with carcinogenesis in multiple tumors. However, the expression pattern and functional effects of ANLN in HNSCC remain to be unclear. Clinical data and online databases were used to analyze the expression of ANLN and its relationship with HNSCC patient survival. Expression of two major splice variants of ANLN was assessed in HNSCC tissues and cell lines. The functional effects and related mechanisms of ANLN isoforms were investigated in HNSCC in vitro and in vivo. Our study showed that patients with high expression of ANLN had a poor prognosis. The two primary isoforms of ANLN transcripts ANLN-201 and ANLN-210 were highly expressed in HNSCC tissues and cell lines. Knockout of ANLN restrained cell proliferation, migration, and invasion of SCC-9 cells. Mechanically, ANLN-201 could interact with c-Myc to keep its protein stability, thereby playing a oncogenic role in HNSCC. ANLN-210 could be transferred to macrophages via exosomes by binding to RNA-binding protein hnRNPC. Exosomal ANLN-210 promoted macrophage polarization via PTEN/PI3K/Akt signaling pathway, thus stimulating tumor growth of HNSCC. ANLN was an independent prognostic factor in patients with HNSCC. Alternatively spliced ANLN isoforms collaboratively promote HNSCC tumorigenesis in vitro and in vivo, which might provide the in-depth role and mechanism of ANLN in HNSCC development.


Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1993 ◽  
Author(s):  
Gabriella Pasqual-Melo ◽  
Thiago Nascimento ◽  
Larissa Juliani Sanches ◽  
Fernanda Paschoal Blegniski ◽  
Julya Karen Bianchi ◽  
...  

Cutaneous squamous cell carcinoma (SCC) is the most prevalent cancer worldwide, increasing the cost of healthcare services and with a high rate of morbidity. Its etiology is linked to chronic ultraviolet (UV) exposure that leads to malignant transformation of keratinocytes. Invasive growth and metastasis are severe consequences of this process. Therapy-resistant and highly aggressive SCC is frequently fatal, exemplifying the need for novel treatment strategies. Cold physical plasma is a partially ionized gas, expelling therapeutic doses of reactive oxygen and nitrogen species that were investigated for their anticancer capacity against SCC in vitro and SCC-like lesions in vivo. Using the kINPen argon plasma jet, a selective growth-reducing action of plasma treatment was identified in two SCC cell lines in 2D and 3D cultures. In vivo, plasma treatment limited the progression of UVB-induced SSC-like skin lesions and dermal degeneration without compromising lesional or non-lesional skin. In lesional tissue, this was associated with a decrease in cell proliferation and the antioxidant transcription factor Nrf2 following plasma treatment, while catalase expression was increased. Analysis of skin adjacent to the lesions and determination of global antioxidant parameters confirmed the local but not systemic action of the plasma anticancer therapy in vivo.


2021 ◽  
Author(s):  
Liaoran Niu ◽  
Wanli Yang ◽  
Wei Zhou ◽  
Lili Duan ◽  
Xiaoqian Wang ◽  
...  

Abstract Background: Proliferation and metastasis are the major malignant phenotypes of esophageal squamous cell carcinoma (ESCC) and the main causes for poor survival in patients with ESCC. Nevertheless, the underlying mechanisms of ESCC proliferation and metastasis remains unclear. The high mobility group box protein family 3 (HMGB3) is one of the HMGB family members. It is critically involved in the occurrence and development of various carcinomas. However, the knowledge of HMGB3 in ESCC remains limited. In this study, we elucidated the role of HMGB3 in ESCC proliferation and metastasis, and the concrete mechanism. Methods: Expression level of HMGB3 and TGF-β interacting factor 2 (TGIF2) in ESCC cell lines and tissues was quantified by qRT-PCR, Western Blot, and immunohistochemistry. In vitro and in vivo assays revealed the functions of TGIF2 and HMGB3 in ESCC. RNA-seq was performed to search for the downstream signaling of HMGB3. ChIP assay and were performed to explore the relationship of HMGB3 and TGIF2. HMGB3-interacting protein was validated by immunoprecipitation.Results: Higher expression of TGIF2 and HMGB3 was observed in ESCC cell lines and tissues and was associated with worse prognosis of ESCC patients. TGIF2 and HMGB3 upregulation could promote ESCC proliferation and metastasis, and vice versa. TGIF2 and HMGB3 upregulation can activate Smad-dependent TGF-β signaling. TGIF2 can transcriptionally regulate HMGB3, and its TGF-β inducing capability and oncogenic role are at least partly HMGB3-dependent. Additionally, TLR3 was identified as a client protein of HMGB3, and their combination might be the reason of TGF-β activation. Conclusions: Collectively, HMGB3-dependent TGIF2 overexpression activates TGF-β signaling and promotes the proliferation and metastasis of ESCC via TLR3 regulation. These findings revealed that TGIF2 and HMGB3 could be prognostic indicators of ESCC and targeting TGIF2/HMGB3/TLR3 axis might improve the OS of ESCC patients.


Nanomedicine ◽  
2019 ◽  
Vol 14 (15) ◽  
pp. 2027-2043 ◽  
Author(s):  
Lei Shi ◽  
Pei Liu ◽  
Jing Wu ◽  
Lun Ma ◽  
Han Zheng ◽  
...  

Aim: To clarify the effectiveness and safety of x-ray-activated photodynamic therapy (X-PDT) for cutaneous squamous cell carcinoma (SCC) and melanoma. Materials & methods: Copper-cysteamine nanoparticles were used as a photosensitizer of X-PDT. The dark toxicity and cytotoxicity were studied in vitro. Tumor volume, microvessel density and acute toxicity of mice were evaluated in vivo. Results: Without x-ray irradiation, copper-cysteamine nanoparticles were nontoxic for keratinocyte cells. XL50 cells (SCC) were more sensitive to X-PDT than B16F10 cells (melanoma). X-PDT successfully inhibited the growth of SCC in vivo (p < 0.05), while the B16F10 melanoma was resistant. Microvessel density in SCC tissue was remarkably reduced (p < 0.05). No obvious acute toxicity reaction was observed. Conclusion: X-PDT is a safe and effective treatment for SCC.


2021 ◽  
Author(s):  
Erliang Guo ◽  
Xionghui Mao ◽  
Lunhua Guo ◽  
Changming An ◽  
Cong Zhang ◽  
...  

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is a common cancer with high mortality. Anilin actin binding protein (ANLN) has been reported to be associated with carcinogenesis in multiple tumors. However, the expression pattern and functional effects of ANLN in HNSCC remains to be unclear.Methods: Expression of two major splice variants of ANLN was assessed in HNSCC tissues and cell lines. The functional effects and related mechanisms of ANLN isoforms were investigated in HNSCC in vitro and in vivo.Results: Our results showed that the two primary isoforms of ANLN transcripts ANLN-201 and ANLN-210 were highly expressed in HNSCC tissues and cell lines. Knockout of ANLN restrained cell proliferation, migration and invasion of SCC-9 cells. Mechanically, ANLN-201 could interact with c-Myc to keep its protein stability, thereby playing a oncogenic role in HNSCC. ANLN-210 could be transferred to macrophages via exosomes by binding to RNA binding protein hnRNPC. Exosomal ANLN-210 promoted macrophage polarization via PTEN/PI3K/Akt signaling pathway, thus stimulating tumor growth of HNSCC.Conclusions: Our findings demonstrate that alternatively spliced ANLN isoforms collaboratively promote HNSCC tumorigenesis in vitro and in vivo, which might provide the in-depth role and mechanism of ANLN in HNSCC development.


1994 ◽  
Vol 111 (3P1) ◽  
pp. 189-196 ◽  
Author(s):  
Carl H. Snyderman ◽  
Ivica Klapan ◽  
Michelle Milanovich ◽  
Dae S. Heo ◽  
Robin Wagner ◽  
...  

Prostaglandin E2 has been identified as an immunosuppressive factor in patients with squamous cell carcinoma of the head and neck. Spontaneous prostaglandin E2 production by 21 cancer cell lines, which were obtained from 17 patients with squamous cell carcinoma of the head and neck, was determined by radioimmunoassay. In comparison with normal keratinocyte cultures, prostaglandin E2 production by cancer cell lines was significantly decreased ( p < 0.0001). Prostaglandin E2 levels demonstrated no correlation to the site, stage, or histo***-pathologic differentiation of the tumor. In a separate group of 17 patients with squamous cell carcinoma of the head and neck, tumor cells were isolated from fresh tumor specimens, and 24-hour PGE2 production in vitro was assayed. No correlation was found with tumor site, stage, or 2-year disease-free survival. Although prostaglandin E2 may have biologic significance in vivo in patients with squamous cell carcinoma of the head and neck, these findings suggest that measurements of tumor cell-derived prostaglandin E2 are not predictive of biologic behavior.


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