GEAMP, a novel gastroesophageal junction carcinoma cell line derived from a malignant pleural effusion

Wei Zhang, Taylor A. Williams, Ankur S. Bhagwath, Jared S. Hiermann, Craig D. Peacock, D. Neil Watkins, Peiguo Ding, Jason Y. Park, Elizabeth A Montgomery, Arlene A. Forastiere, Chunfa Jie, Brandi L. Cantarel, Thai H. Pham, David H. Wang

Research output: Contribution to journalArticle

Abstract

Gastroesophageal junction (GEJ) cancer remains a clinically significant disease in Western countries due to its increasing incidence, which mirrors that of esophageal cancer, and poor prognosis. To develop novel and effective approaches for prevention, early detection, and treatment of patients with GEJ cancer, a better understanding of the mechanisms driving pathogenesis and malignant progression of this disease is required. These efforts have been limited by the small number of available cell lines and appropriate preclinical animal models for in vitro and in vivo studies. We have established and characterized a novel GEJ cancer cell line, GEAMP, derived from the malignant pleural effusion of a previously treated GEJ cancer patient. Comprehensive genetic analyses confirmed a clonal relationship between GEAMP cells and the primary tumor. Targeted next-generation sequencing identified 56 nonsynonymous alterations in 51 genes including TP53 and APC, which are commonly altered in GEJ cancer. In addition, multiple copy-number alterations were found including EGFR and K-RAS gene amplifications and loss of CDKN2A and CDKN2B. Histological examination of subcutaneous flank xenografts in nude and NOD-SCID mice showed a carcinoma with mixed squamous and glandular differentiation, suggesting GEAMP cells contain a subpopulation with multipotent potential. Finally, pharmacologic inhibition of the EGFR signaling pathway led to downregulation of key downstream kinases and inhibition of cell proliferation in vitro. Thus, GEAMP represents a valuable addition to the limited number of bona fide GEJ cancer cell lines.

Original languageEnglish (US)
JournalLaboratory Investigation
DOIs
StatePublished - Jan 1 2019

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Malignant Pleural Effusion
Esophagogastric Junction
Carcinoma
Cell Line
Neoplasms
APC Genes
Inbred NOD Mouse
SCID Mice
Gene Amplification
p53 Genes
Esophageal Neoplasms
Heterografts
Disease Progression
Phosphotransferases
Down-Regulation
Animal Models
Cell Proliferation
Incidence

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Zhang, W., Williams, T. A., Bhagwath, A. S., Hiermann, J. S., Peacock, C. D., Watkins, D. N., ... Wang, D. H. (2019). GEAMP, a novel gastroesophageal junction carcinoma cell line derived from a malignant pleural effusion. Laboratory Investigation. https://doi.org/10.1038/s41374-019-0278-x

GEAMP, a novel gastroesophageal junction carcinoma cell line derived from a malignant pleural effusion. / Zhang, Wei; Williams, Taylor A.; Bhagwath, Ankur S.; Hiermann, Jared S.; Peacock, Craig D.; Watkins, D. Neil; Ding, Peiguo; Park, Jason Y.; Montgomery, Elizabeth A; Forastiere, Arlene A.; Jie, Chunfa; Cantarel, Brandi L.; Pham, Thai H.; Wang, David H.

In: Laboratory Investigation, 01.01.2019.

Research output: Contribution to journalArticle

Zhang, W, Williams, TA, Bhagwath, AS, Hiermann, JS, Peacock, CD, Watkins, DN, Ding, P, Park, JY, Montgomery, EA, Forastiere, AA, Jie, C, Cantarel, BL, Pham, TH & Wang, DH 2019, 'GEAMP, a novel gastroesophageal junction carcinoma cell line derived from a malignant pleural effusion', Laboratory Investigation. https://doi.org/10.1038/s41374-019-0278-x
Zhang, Wei ; Williams, Taylor A. ; Bhagwath, Ankur S. ; Hiermann, Jared S. ; Peacock, Craig D. ; Watkins, D. Neil ; Ding, Peiguo ; Park, Jason Y. ; Montgomery, Elizabeth A ; Forastiere, Arlene A. ; Jie, Chunfa ; Cantarel, Brandi L. ; Pham, Thai H. ; Wang, David H. / GEAMP, a novel gastroesophageal junction carcinoma cell line derived from a malignant pleural effusion. In: Laboratory Investigation. 2019.
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