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Establishment and Characterization of 10 Human Pancreatic Cancer Cell Lines Including a HER2 Overexpressed Cell Line.

ABSTRACT: OBJECTIVE:The incidence of pancreatic adenocarcinoma (PA) approximates its prevalence, as the malignancy is almost consistently fatal within a year. Although the currently available adjuvant therapy seems to provide survival benefit, it is only moderate, and the standard regimen has not yet been established. Therefore, more biological resources to investigate the PA are needed. METHODS:Here, we established and characterized 10 human pancreatic cancer cell lines derived from primary tumor mass. Whole exome sequencing technique was used to identify driver mutations and aberrant pathways in each cell line. RESULTS:Five anticancer drugs were treated to find half maximal effective concentration (EC50), and the response was analyzed in reference to mutational status. Frame shift mutations in ARID1A gene and HER2 amplification were mutually related to better response to the anticancer drugs. In contrast, frame shift mutation in MSH6 gene was associated with resistance to anticancer drugs. CONCLUSIONS:In summary, we established 10 pancreatic cancer cell lines and integrated various molecular aberrations and features of pancreatic cancer cells. Our biological resources are expected to contribute to facilitating research on PA.

SUBMITTER: Kim SC

PROVIDER: S-EPMC6867661 | biostudies-literature | 2019 Nov/Dec

REPOSITORIES: biostudies-literature

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Establishment and Characterization of 10 Human Pancreatic Cancer Cell Lines Including a HER2 Overexpressed Cell Line.

Kim Soon-Chan SC Shin Young-Kyoung YK Kim Sun-Whe SW Seo Ha-Young HY Kwon Wooil W Kim Hongbeom H Han Youngmin Y Lee Ja-Oh JO Jang Jin-Young JY Ku Ja-Lok JL

Pancreas 20191101 10

<h4>Objective</h4>The incidence of pancreatic adenocarcinoma (PA) approximates its prevalence, as the malignancy is almost consistently fatal within a year. Although the currently available adjuvant therapy seems to provide survival benefit, it is only moderate, and the standard regimen has not yet been established. Therefore, more biological resources to investigate the PA are needed.<h4>Methods</h4>Here, we established and characterized 10 human pancreatic cancer cell lines derived from primar ...[more]

PMID: 31688591

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Project description:BackgroundCanine mammary tumors (CMTs) have a poor prognosis, along with tumor recurrence and metastasis. Cell lines are vital in vitro models for CMT research. Many CMT epithelial cell lines were reported. However, canine mammary myoepithelial cells, the contractile component of the canine mammary tissue were overlooked. This study aimed at establishing such a cell line. CMT-1 cell line was obtained from a canine mammary tumor CMT-1 and characterized molecularly through qPCR, western blotting, immunochemistry and immunofluorescence. Its doubling time, cytogenetic analysis and migration rate were evaluated using growth study, karyotype analysis and wound healing assay respectively. To determine its tumorigenesis, xenograft transplantation was performed.ResultsCMT-1 tumor was a complex canine mammary carcinoma that stained negative to estrogen receptors (ER) and progesterone receptors (PR), but positive to human epidermal growth receptor-2 (HER2), defined as HER2-enriched subtype. In this study, a CMT-1 cell line obtained from CMT-1 tumor was immune-positive to vimentin, α-SMA, p63 and negative to E-cadherin (E-cad), indicating CMT-1 cells were myoepithelial cells. It was successfully cultured for more than 50 passages showing the same immunoreactivity to ER, PR, and HER2 as the primary canine tumor. The doubling time of CMT-1 cell line was 26.67 h. The chromosome number of CMT-1 cells ranged from 31 to 64. A potential spontaneous epithelial to mesenchymal transition (EMT) was noticed during cell cultures. Potential EMT-induced CMT-1 cells showed no significance in migration rate compared to the original CMT-1 cells. CMT-1 cells was able to grow on a 3D culture and formed grape-like, solid, and cystic mammospheres at different time period. Inoculation of CMT-1 cells induced a complex HER2-enriched mammary tumor with metastasis in mice.ConclusionsA canine cancerous HER2-enriched myoepithelial cell line was successfully established and a canine mammosphere developed from myoepithelial cells was documented in this study. We are expecting this novel cell line and its associated mammospheres could be used as a model to elucidate the role of myoepithelial cells in CMT carcinogensis in the future.

Dataset Information

Establishment and Characterization of 10 Human Pancreatic Cancer Cell Lines Including a HER2 Overexpressed Cell Line.

Publications

Establishment and Characterization of 10 Human Pancreatic Cancer Cell Lines Including a HER2 Overexpressed Cell Line.

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