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, Hyun Cheol Chung, Sun Young Rha

Research output: Contribution to journalArticle

5 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, Hyun Cheol ; Rha, Sun Young. / 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, Hyun Cheol; Rha, Sun Young.

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

Research output: Contribution to journalArticle

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