Forty-nine gastric cancer cell lines with integrative genomic profiling for development of c-MET inhibitor

Hyun Jeong Kim, Sun Kyoung Kang, Woo Sun Kwon, Tae Soo Kim, Inhye Jeong, Hei Cheul Jeung, Michael Kragh, Ivan D. Horak, Hyuncheol Chung, SunYoung Rha

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Receptor tyrosine kinase MET (c-MET) has received considerable attention as a potential target for gastric cancer (GC) therapy and a number of c-MET inhibitors have been developed. For successful drug development, proper preclinical studies especially using patient derived cancer cell lines are very important. We profiled MET and MET-related characteristics in 49 GC cell lines to utilize them as models in preclinical studies of GC. Forty-nine cell lines were analyzed for genetic, biological, and molecular status to characterize MET and MET-related molecules. Four c-MET inhibitors were tested to elucidate the dependency on MET pathway in the 49 GC cell lines. Six of 49 cell lines were MET amplified with overexpression of c-MET and p-MET. The variants of MET were not associated with c-MET expression or amplification. Hs746T showed an exon 14 deletion in conjunction with MET amplification. The cell lines were divided into 6 MET amplified, 2 c-MET overexpressed, 2 hepatocyte growth factor (HGF) overexpressed, and 39 MET-negative subgroups. Except tivantinib, the c-MET inhibitors showed higher inhibition (%) in MET amplified than in MET nonamplified cell lines that MET amplified cell lines showed MET pathway dependency. However, the c-MET overexpressed and HGF overexpressed cell lines showed moderate dependency on MET pathway. Well-characterized cell lines are very important in studying drug development. Our 49 GC cell lines had various characteristics of MET and MET-related molecules and MET pathway dependency. These provide a promising platform for development of various RTK inhibitors including c-MET inhibitors.

Original languageEnglish
Pages (from-to)151-159
Number of pages9
JournalInternational Journal of Cancer
Volume143
Issue number1
DOIs
Publication statusPublished - 2018 Jul 1

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Stomach Neoplasms
Cell Line
Hepatocyte Growth Factor
Proto-Oncogene Proteins c-met
Pharmaceutical Preparations
Molecular Biology
Exons

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kim, Hyun Jeong ; Kang, Sun Kyoung ; Kwon, Woo Sun ; Kim, Tae Soo ; Jeong, Inhye ; Jeung, Hei Cheul ; Kragh, Michael ; Horak, Ivan D. ; Chung, Hyuncheol ; Rha, SunYoung. / Forty-nine gastric cancer cell lines with integrative genomic profiling for development of c-MET inhibitor. In: International Journal of Cancer. 2018 ; Vol. 143, No. 1. pp. 151-159.
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abstract = "Receptor tyrosine kinase MET (c-MET) has received considerable attention as a potential target for gastric cancer (GC) therapy and a number of c-MET inhibitors have been developed. For successful drug development, proper preclinical studies especially using patient derived cancer cell lines are very important. We profiled MET and MET-related characteristics in 49 GC cell lines to utilize them as models in preclinical studies of GC. Forty-nine cell lines were analyzed for genetic, biological, and molecular status to characterize MET and MET-related molecules. Four c-MET inhibitors were tested to elucidate the dependency on MET pathway in the 49 GC cell lines. Six of 49 cell lines were MET amplified with overexpression of c-MET and p-MET. The variants of MET were not associated with c-MET expression or amplification. Hs746T showed an exon 14 deletion in conjunction with MET amplification. The cell lines were divided into 6 MET amplified, 2 c-MET overexpressed, 2 hepatocyte growth factor (HGF) overexpressed, and 39 MET-negative subgroups. Except tivantinib, the c-MET inhibitors showed higher inhibition ({\%}) in MET amplified than in MET nonamplified cell lines that MET amplified cell lines showed MET pathway dependency. However, the c-MET overexpressed and HGF overexpressed cell lines showed moderate dependency on MET pathway. Well-characterized cell lines are very important in studying drug development. Our 49 GC cell lines had various characteristics of MET and MET-related molecules and MET pathway dependency. These provide a promising platform for development of various RTK inhibitors including c-MET inhibitors.",
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Forty-nine gastric cancer cell lines with integrative genomic profiling for development of c-MET inhibitor. / Kim, Hyun Jeong; Kang, Sun Kyoung; Kwon, Woo Sun; Kim, Tae Soo; Jeong, Inhye; Jeung, Hei Cheul; Kragh, Michael; Horak, Ivan D.; Chung, Hyuncheol; Rha, SunYoung.

In: International Journal of Cancer, Vol. 143, No. 1, 01.07.2018, p. 151-159.

Research output: Contribution to journalArticle

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AU - Jeung, Hei Cheul

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