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Article

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

by
Maria Bååth
1,
Jenny-Maria Jönsson
1,
Sofia Westbom Fremer
1,2,
Laura Martín de la Fuente
1,
Lena Tran
1,
Susanne Malander
1,
Päivi Kannisto
3,
Anna Måsbäck
2,
Gabriella Honeth
1 and
Ingrid Hedenfalk
1,*
1
Division of Oncology, Department of Clinical Sciences Lund, Lund University and Skåne University Hospital, 223 81 Lund, Sweden
2
Department of Surgical Pathology, Division of Laboratory Medicine, Skåne University Hospital, 222 42 Lund, Sweden
3
Division of Obstetrics and Gynaecology, Department of Clinical Sciences Lund, Lund University and Skåne University Hospital, 222 42 Lund, Sweden
*
Author to whom correspondence should be addressed.
Genes 2021, 12(5), 742; https://doi.org/10.3390/genes12050742
Submission received: 14 April 2021 / Revised: 6 May 2021 / Accepted: 12 May 2021 / Published: 14 May 2021
(This article belongs to the Special Issue Advances in Genetics and Genomics of Ovarian Cancer)
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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.
Keywords: HGSC; cancer stem cells; SOX2; MET; OCT4; ovarian cancer; PARP HGSC; cancer stem cells; SOX2; MET; OCT4; ovarian cancer; PARP

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MDPI and ACS Style

Bååth, M.; Jönsson, J.-M.; Westbom Fremer, S.; Martín de la Fuente, L.; Tran, L.; Malander, S.; Kannisto, P.; Måsbäck, A.; Honeth, G.; Hedenfalk, I. MET Expression and Cancer Stem Cell Networks Impact Outcome in High-Grade Serous Ovarian Cancer. Genes 2021, 12, 742. https://doi.org/10.3390/genes12050742

AMA Style

Bååth M, Jönsson J-M, Westbom Fremer S, Martín de la Fuente L, Tran L, Malander S, Kannisto P, Måsbäck A, Honeth G, Hedenfalk I. MET Expression and Cancer Stem Cell Networks Impact Outcome in High-Grade Serous Ovarian Cancer. Genes. 2021; 12(5):742. https://doi.org/10.3390/genes12050742

Chicago/Turabian Style

Bååth, Maria, Jenny-Maria Jönsson, Sofia Westbom Fremer, Laura Martín de la Fuente, Lena Tran, Susanne Malander, Päivi Kannisto, Anna Måsbäck, Gabriella Honeth, and Ingrid Hedenfalk. 2021. "MET Expression and Cancer Stem Cell Networks Impact Outcome in High-Grade Serous Ovarian Cancer" Genes 12, no. 5: 742. https://doi.org/10.3390/genes12050742

APA Style

Bååth, M., Jönsson, J.-M., Westbom Fremer, S., Martín de la Fuente, L., Tran, L., Malander, S., Kannisto, P., Måsbäck, A., Honeth, G., & Hedenfalk, I. (2021). MET Expression and Cancer Stem Cell Networks Impact Outcome in High-Grade Serous Ovarian Cancer. Genes, 12(5), 742. https://doi.org/10.3390/genes12050742

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