Establishment and genetic characterization of six unique tumor cell lines as preclinical models for sinonasal squamous cell carcinoma

Abstract

Sinonasal squamous cell carcinomas (SCC) are rare tumors, etiologically related to occupational exposure to wood and leather dust. In spite of surgical and radiotherapeutic advances, the 5 year survival is still 30–50%. Therefore, alternative treatment options are needed. We report the establishment and characterization of six unique human sinonasal SCC cell lines, named SCCNC1, 2, 4, 5, 6 and 7. In vitro growth and invasion characteristics were evaluated and genetic profiles were compared to those of the original primary tumors. The population doubling times ranged from 21 to 34 hours. Cell lines SCCNC2 and 7 were highly invasive in matrigel. Five cell lines carried a high number of copy number alterations, including amplifications and homozygous deletions, while one showed only three abnormalities. Sequence analysis revealed three cell lines with TP53 mutation and none with KRAS or BRAF. Overexpression of p53 was observed in five, and of EGFR in four cell lines. None of the cell lines showed strong immunopositivity of p16 or presence of human papilloma virus. In conclusion, we have created six new cell lines that are clinically and genetically representative of sinonasal SCC and that will be a useful tool for the preclinical testing of new therapeutic agents.

Aberrant Expression Profile of Long Noncoding RNA in Human Sinonasal Squamous Cell Carcinoma by Microarray Analysis

“…The KEGG pathway analysis identified that many pathways were related to cancer, such as microRNAs in cancer, P53 signaling pathway, PI3K-Akt signaling pathway. For example, it has been documented that the p53 signaling pathway is activated in many solid tumors, including SSCC [1, 16, 17]. In the present study, p53 signaling pathway was related to lncRNA NONHSAT125629.…”

“…Sinonasal squamous cell carcinomas (SSCC) are rare tumor, estimated to account for approximately 3–6% of all head and neck squamous cell carcinomas. SSCC originate in the respiratory epithelium of the sinonasal cavities [1]. Approximately 60% of SSCC arise in the maxillary sinus, 20–30% in the nasal cavity, 10–15% in the ethmoid sinuses, and ~1% in the frontal and sphenoid sinuses [2, 3].…”

“…The low incidence of SSCC combined with their nonspecific symptoms often leads to a critical delay in diagnosis. Treatment for SSCC is usually primarily surgical with adjuvant radiotherapy and sometimes with adjuvant chemotherapy for all except small tumors [1]. Surgical management of SSCC is of great challenge due to its anatomical complexity, especially advanced SSCC involving eye, skull base, or infratemporal fossa.…”

“…Surgical management of SSCC is of great challenge due to its anatomical complexity, especially advanced SSCC involving eye, skull base, or infratemporal fossa. In spite of major advances in the therapy of SSCC, including surgery and chemoradiotherapy methods, the 5-year survival rate is still very low (30–50%) [1]. …”

High-Frequency Targetable EGFR Mutations in Sinonasal Squamous Cell Carcinomas Arising from Inverted Sinonasal Papilloma

“…The SCCNC4 cell line was obtained from the laboratory of Dr. Mario A. Hermsen. This cell line was derived from a 73-year-old female with SNSCC of the right maxillary sinus who had previously been treated for an ISP involving the right nasal cavity (7). Sanger sequencing demonstrated an EGFR N771_H773dup mutation in UM-SCC-112 cells as well in FFPE resection material from which this cell line was derived.…”