PS02.194: THE GENERATION & VALIDATION OF FOUR NEW ESOPHAGEAL CANCER CELL LINES WITH MATCHED PATIENT-DERIVED TUMOR XENOGRAFTS. (14th September 2018)

• Record Type: Journal Article
• Authors: Read, Matthew; Liu, David; Guerra, Glen; Duong, Cuong; Krishnadath, Kausilia; Clemons, Nicholas; Phillips, Wayne
• Is Part Of: Diseases of the esophagus. Volume 31(2018)Supplement 1
• Page Start: 177
• Page End: 177
• Publication Date: 2018-09-14
• Subjects: Metastatic Model -- Cancer Cell Lines -- Esophageal adenocarcinoma -- Esophageal SCC; Esophagus -- Diseases -- Periodicals; 616.32
• DOI: 10.1093/dote/doy089.PS02.194
• Languages: English
• ISSNs: 1120-8694

Abstract

Abstract: Background: Research into esophageal cancer, in particular adenocarcinoma, has been hampered by a paucity of relevant pre-clinical models. To date, only 13 bona fide adenocarcinoma cell lines have been published, with only six being derived from patients with confirmed Barrett's esophagus. Having so few available cell lines makes it difficult to model the genetic diversity observed in esophageal adenocarcinoma. In addition, only one of these lines has been shown to be reproducibly metastatic in xenograft models. This is in distinct contrast to the disease in the human, which is almost universally metastatic when left untreated. Methods: Using our previously published intramuscular xenografting technique 1, patient derived tumour xenografts (PDTX) were generated from endoscopic biopsies of treatment naïve esophageal adenocarcinoma and SCC biopsies. Following successful engraftment, PDTX tissue was digested in order to generate small explant pieces. Explants were then plated with media and cultured for extended periods until a dominant clone was cultured. One cell line was directly obtained from the malignant ascites of a mouse that was harboring a PDTX that had metastasized. Established cell lines then underwent validation, which consisted of short tandem repeat (STR) analysis, targeted oncogene assessment using the Illumina TruSeq cancer panel, tumorigenic assay, immunohistochemical (IHC) analysis for both adenocarcinoma and SCC markers as well as FACS analysis for both epithelial and human markers. Results: Matched PDTX and xenograft derived cell lines were generated from two separate SCCs in addition to two separate adenocarcinomas. From one of the adenocarcinoma lines, two separate cell lines were generated, with one clone demonstrating a reproducibly metastatic phenotype, while the other remained non-metastatic. STR analysis confirmed all of the PDTXs and cell lines were derived from their respective patients and IHC analysis confirmed that they expressed the appropriate epithelial markers. Conclusion: We have successfully generated and validated four additional esophageal cancer cell lines (two adenocarcinoma and two SCC) with matched PDTXs. The combination of both models creates a powerful tool, given the ability of PDTXs to recapitulate the heterogeneity and stromal elements of the original tumour, and the versatility of cell lines for mechanistic studies. 1. Read, M., et al. Annals of surgical oncology 2015. Disclosure: All authors have declared no conflicts of interest.