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MET Expression and Cancer Stem Cell Networks Impact Outcome in High-Grade Serous Ovarian Cancer

Bååth, Maria LU ; Jönsson, Jenny-Maria LU ; Westbom Fremer, Sofia LU orcid ; Martin de la Fuente, Laura LU ; Tran, Lena LU ; Malander, Susanne LU orcid ; Kannisto, Päivi LU ; Måsbäck, Anna LU ; Honeth, Gabriella LU and Hedenfalk, Ingrid LU orcid (2021) In Genes 12(5).
Abstract
Overexpression of the receptor tyrosine kinase MET has been linked to poor survival in several cancer types, and MET has been suggested to interact with stem cell networks. In vitro studies have further suggested a possible benefit of a combined treatment using PARP and MET inhibitors. We used a tissue microarray (TMA) with 130 samples of advanced-stage high-grade serous fallopian tube/ovarian cancer (HGSC) to investigate the prognostic value of MET protein expression alone and in combination with the stem cell factor SOX2. The possible synergistic effects of a PARP and MET inhibitor treatment were evaluated in two cell lines with BRCA1 or BRCA2 deficiency and in their BRCA1/2-proficient counterparts. Patients with tumors positive for MET... (More)
Overexpression of the receptor tyrosine kinase MET has been linked to poor survival in several cancer types, and MET has been suggested to interact with stem cell networks. In vitro studies have further suggested a possible benefit of a combined treatment using PARP and MET inhibitors. We used a tissue microarray (TMA) with 130 samples of advanced-stage high-grade serous fallopian tube/ovarian cancer (HGSC) to investigate the prognostic value of MET protein expression alone and in combination with the stem cell factor SOX2. The possible synergistic effects of a PARP and MET inhibitor treatment were evaluated in two cell lines with BRCA1 or BRCA2 deficiency and in their BRCA1/2-proficient counterparts. Patients with tumors positive for MET had worse overall survival (log-rank test, p = 0.015) compared to patients with MET-negative tumors. The prognostic role of MET was even more prominent in the subgroup of patients with SOX2-negative tumors (p = 0.0081). No synergistic effects of the combined treatment with PARP and MET inhibitors were found in the cell lines examined. We conclude that MET expression could be used as a marker for OS in HGSC and that stemness should be taken into consideration when evaluating the mechanisms of this effect. (Less)
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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes
volume
12
issue
5
article number
742
publisher
MDPI AG
external identifiers
  • pmid:34069138
  • pmid:34069138
  • scopus:85106940189
ISSN
2073-4425
DOI
10.3390/genes12050742
language
English
LU publication?
yes
id
92dc6bb0-543a-4cc3-aae7-9d6470d5d3a2
date added to LUP
2021-05-19 13:56:46
date last changed
2024-06-01 10:42:59
@article{92dc6bb0-543a-4cc3-aae7-9d6470d5d3a2,
  abstract     = {{Overexpression of the receptor tyrosine kinase MET has been linked to poor survival in several cancer types, and MET has been suggested to interact with stem cell networks. In vitro studies have further suggested a possible benefit of a combined treatment using PARP and MET inhibitors. We used a tissue microarray (TMA) with 130 samples of advanced-stage high-grade serous fallopian tube/ovarian cancer (HGSC) to investigate the prognostic value of MET protein expression alone and in combination with the stem cell factor SOX2. The possible synergistic effects of a PARP and MET inhibitor treatment were evaluated in two cell lines with BRCA1 or BRCA2 deficiency and in their BRCA1/2-proficient counterparts. Patients with tumors positive for MET had worse overall survival (log-rank test, p = 0.015) compared to patients with MET-negative tumors. The prognostic role of MET was even more prominent in the subgroup of patients with SOX2-negative tumors (p = 0.0081). No synergistic effects of the combined treatment with PARP and MET inhibitors were found in the cell lines examined. We conclude that MET expression could be used as a marker for OS in HGSC and that stemness should be taken into consideration when evaluating the mechanisms of this effect.}},
  author       = {{Bååth, Maria and Jönsson, Jenny-Maria and Westbom Fremer, Sofia and Martin de la Fuente, Laura and Tran, Lena and Malander, Susanne and Kannisto, Päivi and Måsbäck, Anna and Honeth, Gabriella and Hedenfalk, Ingrid}},
  issn         = {{2073-4425}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{5}},
  publisher    = {{MDPI AG}},
  series       = {{Genes}},
  title        = {{MET Expression and Cancer Stem Cell Networks Impact Outcome in High-Grade Serous Ovarian Cancer}},
  url          = {{http://dx.doi.org/10.3390/genes12050742}},
  doi          = {{10.3390/genes12050742}},
  volume       = {{12}},
  year         = {{2021}},
}