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In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System
Published on: January 9, 2020
Establishment and characterization of novel cell lines from sinonasal undifferentiated carcinoma
Yoko Takahashi1, Michael E Kupferman, Diana Bell
1Department of Head and Neck Surgery and Pathology, The University of Texas MD Anderson Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Purpose:
Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer. Despite the use of multimodality treatment, the overall prognosis remains poor. To better understand the biologic features of SNUC and help develop new therapies for the disease, we established SNUC cell lines and characterized their biologic behaviors.
Experimental Design:
Cell lines were established from a patient with a T4N0M0 SNUC of the right maxillary sinus who was treated with surgical resection at our center. Tumor colonies were harvested and were sequentially replated onto larger plates. Two populations were developed and labeled MDA8788-6 and MDA8788-7. These cell lines were characterized with molecular, biomarker, functional, and histologic analyses.
Results:
Short tandem repeat genotyping revealed that the cell line is isogenic to the parental tumor, and cytogenetic analysis identified 12 chromosomal translocations. The SNUC cell lines do not form colonies in soft agar but are tumorigenic and nonmetastatic in an orthotopic mouse model of sinonasal cancer. Western blot analysis revealed that both MDA8788 cell lines express epithelial markers but do not express mesenchymal markers or the endocrine marker synaptophysin.
Conclusions:
This is the first report of the establishment of stable human-derived SNUC cell lines. The lines were highly tumorigenic and maintain the histologic and molecular features of the original tumor. These cell lines should serve as useful tools for the future study of SNUC biology and the development and testing of novel therapies for this deadly disease.
Insights
Researchers established new human cell lines for sinonasal undifferentiated carcinoma (SNUC), a rare cancer. These cell lines are tumorigenic and retain original tumor features, aiding future SNUC therapy development.
Area of Science:
- Oncology
- Cancer Biology
- Cell Line Development
Background:
- Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy with a poor prognosis despite multimodal treatment.
- Understanding the biological characteristics of SNUC is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To establish and characterize novel human-derived cell lines from SNUC.
- To provide valuable tools for investigating SNUC biology and facilitating the development of new treatments.
Main Methods:
- Cell lines (MDA8788-6 and MDA8788-7) were derived from a patient with T4N0M0 SNUC.
- Characterization involved molecular, biomarker, functional, and histological analyses, including cytogenetic and Western blot analyses.
- Tumorigenicity and metastatic potential were assessed using an orthotopic mouse model.
Main Results:
- The established SNUC cell lines are isogenic to the parental tumor and exhibit 12 chromosomal translocations.
- While non-metastatic, the cell lines are tumorigenic in vivo and express epithelial markers but not mesenchymal or endocrine markers.
- The cell lines did not form colonies in soft agar, indicating anchorage-independent growth limitations.
Conclusions:
- This study reports the first successful establishment of stable, human-derived SNUC cell lines.
- These cell lines maintain the histological and molecular characteristics of the original tumor.
- The developed cell lines represent a significant resource for future research into SNUC pathogenesis and therapeutic interventions.
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