ArticlePloS one2013
Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- Allosteric Anti-KLK4 Antibody Development for Targeted Anti-cancer Effects in Ovarian Carcinoma.Journal of molecular biology · 2025Article
- Assessing Auranofin for Second-Line Use in Chemoresistant Ovarian Cancer: Effects on Tumour Spheroid and Primary Cell Growth.Journal of cellular and molecular medicine · 2025Article
- Cancer-mesothelial and cancer-macrophage interactions in the ovarian cancer microenvironment.American journal of physiology. Cell physiology · 2023Review
- Remodelling of the tumour microenvironment by the kallikrein-related peptidases.Nature reviews. Cancer · 2022Review
- Role of Serine Proteases at the Tumor-Stroma Interface.Frontiers in immunology · 2022Review
- Angiogenesis-related non-coding RNAs and gastrointestinal cancer.Molecular therapy oncolytics · 2021Review
- Carboplatin sensitivity in epithelial ovarian cancer cell lines: The impact of model systems.PloS one · 2020Article
- Uncoupling Traditional Functionalities of Metastasis: The Parting of Ways with Real-Time Assays.Journal of clinical medicine · 2019Review
- Reversing platinum resistance in ovarian cancer multicellular spheroids by targeting Bcl-2.OncoTargets and therapy · 2019Article
- Long non-coding RNA LINC01314 represses cell migration, invasion, and angiogenesis in gastric cancer via the Wnt/β-catenin signaling pathway by down-regulating KLK4.Cancer cell international · 2019Article
- Article
- Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in serous ovarian cancer.British journal of cancer · 2018Article
- Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms.Biological chemistry · 2018Article
- The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices.International journal of molecular sciences · 2018Article
- Review
- High-throughput 3-dimensional culture of epithelial ovarian cancer cells as preclinical model of disease.Oncotarget · 2018Article
- Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in prostate-derived stromal cells.Molecular oncology · 2017Article
- Mesothelial cells interact with tumor cells for the formation of ovarian cancer multicellular spheroids in peritoneal effusions.Clinical & experimental metastasis · 2016Article
- Direct and indirect mechanisms of KLK4 inhibition revealed by structure and dynamics.Scientific reports · 2016Article
- PLGA nanoparticle encapsulation reduces toxicity while retaining the therapeutic efficacy of EtNBS-PDT in vitro.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High tumor kallikrein-related-peptidase 4 (KLK4) levels are associated with a poor outcome for women with serous epithelial ovarian cancer (EOC), for which peritoneal dissemination and chemoresistance are key events. To determine the role of KLK4 in these events, we examined KLK4-transfected SKOV-3 and endogenous KLK4 expressing OVCA432 cells in 3-dimensional (3D) suspension culture to mimic the ascites microenvironment. KLK4-SKOV-3 cells formed multicellular aggregates (MCAs) as seen in ascites, as did SKOV-3 cells treated with active KLK4. MCA formation was reduced by treatment with a KLK4 blocking antibody or the selective active site KLK4 sunflower trypsin inhibitor (SFTI-FCQR). KLK4-MCAs formed larger cancer cell foci in mesothelial cell monolayers than those formed by vector and native SKOV-3 cells, suggesting KLK4-MCAs are highly invasive in the peritoneal microenvironment. A high level of KLK4 is expressed by ascitic EOC cells compared to matched primary tumor cells, further supporting its role in the ascitic microenvironment. Interestingly, KLK4 transfected SKOV-3 cells expressed high levels of the KLK4 substrate, urokinase plasminogen activator (uPA), particularly in 3D-suspension, and high levels of both KLK4 and uPA were observed in patient cells taken from ascites. Importantly, the KLK4-MCAs were paclitaxel resistant which was reversed by SFTI-FCQR and to a lesser degree by the general serine protease inhibitor, Aprotinin, suggesting that in addition to uPA, other as yet unidentified substrates of KLK4 must be involved. Nonetheless, these data suggest that KLK4 inhibition, in conjunction with paclitaxel, may improve the outcome for women with serous epithelial ovarian cancer and high KLK4 levels in their tumors.
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