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Peer-reviewedCC BY 4.0Cancers

Kallikrein-Related Peptidase 5 Is Associated with Tumor Progression, KRT19 Expression, and Distinct Molecular Programs in High-Grade Serous Ovarian Cancer

  • Sophia Bielesch1
  • Antonia Blechschmidt1
  • Georgia Lachanioti1,2
  • Johanna Moeller1
  • Gregor Bielesch3
  • Sophia Fella1
  • Dalila Darmoul4
  • Stefan Tholen5
  • Oliver Schilling5
  • Holger Bronger1,6
  • Marion Kiechle1
  • Viktor Magdolen1
1 more authors
  • Tobias Dreyer1,6
6 affiliations
  1. 1Department of Gynecology and Obstetrics, TUM University Hospital, 81675 Munich, Germany
  2. 2Laboratory of Clinical Biochemistry—Molecular Diagnostics, Second Department of Pediatrics, “P. & A. Kyriakou” Children’s Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
  3. 3Department of Trauma Surgery, TUM University Hospital, 81675 Munich, Germany
  4. 4Institut de Biologie Paris Seine, CNRS UMR8263-INSERM U1345, Sorbonne Université, 75005 Paris, France
  5. 5Institute for Surgical Pathology, Medical Center, University of Freiburg, 79098 Freiburg, Germany
  6. 6German Cancer Consortium (DKTK), Partner Site Munich (A Partnership Between DKFZ and Technical University of Munich), 69120 Heidelberg, Germany
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Abstract

Background/Objectives: High-grade serous ovarian cancer (HGSOC) is characterized by peritoneal dissemination and ascites formation. Kallikrein-related peptidase 5 (KLK5) has been linked to aggressive disease. Building on evidence linking KLK4–7 to keratin 19 (KRT19), we hypothesized that a KLK5–KRT19 axis contributes to tumor progression and investigated this potential axis alongside broader KLK5-associated tumor-cell, metabolic, signaling, and microenvironmental mechanisms. Methods: KLK5-overexpressing ovarian cancer models were characterized using functional assays (adhesion, migration, spheroid formation), KRT19 expression analysis, proteomics, and gene set enrichment analysis. The putative KRT19–KLK5 axis was further investigated in vivo, in silico, and by immunohistochemistry. KLK5-dependent tumor progression was assessed in vivo, including survival and ascites formation, with quantification of CXCL9 in ascitic fluid. Clinical relevance was evaluated by immunohistochemistry in an HGSOC cohort. Results: In vitro, KLK5 overexpression induced KRT19 expression and enhanced spheroid formation, whereas effects on adhesion and migration were limited. Proteomic analysis identified KLK5-associated alterations in cholesterol homeostasis, coagulation, and mTORC1 signaling. In the in vivo mouse model, KLK5 overexpression was associated with reduced survival and increased ascites formation, and KLK5 induced intratumoral KRT19 expression. KLK5 and KRT19 protein levels were positively associated in patient tumors and primary ascites-derived tumor cells. In ascites, KLK5 overexpression was associated with reduced CD3+ cell abundance and lower CXCL9 concentrations. Conclusions: KLK5 promotes HGSOC progression. Its association with KRT19 expression, altered cholesterol homeostasis and mTORC1 signaling, reduced CD3+ cells and CXCL9 in ascites suggests that KLK5 contributes to both tumor-cell and immune features of HGSOC.

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Cite

BibTeXRIS
BibTeX
@article{bielesch2026kallikreinrelated,
  title = {{Kallikrein-Related Peptidase 5 Is Associated with Tumor Progression, KRT19 Expression, and Distinct Molecular Programs in High-Grade Serous Ovarian Cancer}},
  author = {Sophia Bielesch and Antonia Blechschmidt and Georgia Lachanioti and Johanna Moeller and Gregor Bielesch and Sophia Fella and Dalila Darmoul and Stefan Tholen and Oliver Schilling and Holger Bronger and Marion Kiechle and Viktor Magdolen and Tobias Dreyer},
  journal = {Cancers},
  year = {2026},
  month = oct,
  doi = {10.3390/cancers18203387},
  url = {https://www.mdpi.com/2072-6694/18/20/3387},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Kallikrein-Related Peptidase 5 Is Associated with Tumor Progression, KRT19 Expression, and Distinct Molecular Programs in High-Grade Serous Ovarian Cancer
AU  - Sophia Bielesch
AU  - Antonia Blechschmidt
AU  - Georgia Lachanioti
AU  - Johanna Moeller
AU  - Gregor Bielesch
AU  - Sophia Fella
AU  - Dalila Darmoul
AU  - Stefan Tholen
AU  - Oliver Schilling
AU  - Holger Bronger
AU  - Marion Kiechle
AU  - Viktor Magdolen
AU  - Tobias Dreyer
PY  - 2026
DA  - 2026/10/01
JO  - Cancers
DO  - 10.3390/cancers18203387
UR  - https://www.mdpi.com/2072-6694/18/20/3387
AB  - Background/Objectives: High-grade serous ovarian cancer (HGSOC) is characterized by peritoneal dissemination and ascites formation. Kallikrein-related peptidase 5 (KLK5) has been linked to aggressive disease. Building on evidence linking KLK4–7 to keratin 19 (KRT19), we hypothesized that a KLK5–KRT19 axis contributes to tumor progression and investigated this potential axis alongside broader KLK5-associated tumor-cell, metabolic, signaling, and microenvironmental mechanisms. Methods: KLK5-overexpressing ovarian cancer models were characterized using functional assays (adhesion, migration, spheroid formation), KRT19 expression analysis, proteomics, and gene set enrichment analysis. The putative KRT19–KLK5 axis was further investigated in vivo, in silico, and by immunohistochemistry. KLK5-dependent tumor progression was assessed in vivo, including survival and ascites formation, with quantification of CXCL9 in ascitic fluid. Clinical relevance was evaluated by immunohistochemistry in an HGSOC cohort. Results: In vitro, KLK5 overexpression induced KRT19 expression and enhanced spheroid formation, whereas effects on adhesion and migration were limited. Proteomic analysis identified KLK5-associated alterations in cholesterol homeostasis, coagulation, and mTORC1 signaling. In the in vivo mouse model, KLK5 overexpression was associated with reduced survival and increased ascites formation, and KLK5 induced intratumoral KRT19 expression. KLK5 and KRT19 protein levels were positively associated in patient tumors and primary ascites-derived tumor cells. In ascites, KLK5 overexpression was associated with reduced CD3+ cell abundance and lower CXCL9 concentrations. Conclusions: KLK5 promotes HGSOC progression. Its association with KRT19 expression, altered cholesterol homeostasis and mTORC1 signaling, reduced CD3+ cells and CXCL9 in ascites suggests that KLK5 contributes to both tumor-cell and immune features of HGSOC.
SN  - 2072-6694
ER  -