Pospichalova Lab

Harnessing the potential of ascites to improve outcomes for ovarian cancer patients through innovative research

Extracellular vesicles in ovarian cancer and the potential of malignant ascites for ovarian cancer research

Ovarian cancer (OC) ranks among the deadliest cancers in women. Lack of symptoms, rapid metastases and common chemoresistance contribute to unfortunate fate of majority of OC patients, especially those having high-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common and most aggressive type of OC. Many HGSC patients have excess fluid in the peritoneum called ascites. Ascites is basically a tumor microenvironment (TME) containing various cells, proteins and extracellular vesicles (EVs).

EVs play an important role in cancerogenesis and hold great promise as disease biomarkers, yet their small size and polydispersity bring various challenges to their isolation and characterization, including method-dependent enrichment of different EV subtypes as well as contaminants.

Our research projects focus on method development in the EV field, comparison of different isolation methods and especially on proteomic analyses of ascitic EVs and how these can help in unraveling the underlying molecular principles of disease progression and how can ascites serve as a new source of diagnostic/screening/prognostic EV-based biomarkers of HGSC and clinically relevant disease models, such as organoids.

We are proud members of the International Society for Extracellular Vesicles (ISEV) and co-founders of Czech Society for Extracellular Vesicles (CzeSEV).

Research

Ovarian cancer

Ovarian cancer is a deadly gynecologic cancer, often diagnosed late due to a lack of early symptoms and effective screening. High-grade serous carcinoma (HGSC), its most aggressive form, poses challenges like rapid spread and chemoresistance. Research is vital to develop early detection, improve treatments, and ultimately save lives.

Extracellular Vesicles (EVs):

Extracellular vesicles (EVs) are small particles released by cells that carry proteins, lipids, and genetic material. In cancer, EVs play a key role in communication between tumor cells and their environment, promoting growth and spread. Their unique cargo makes them promising as biomarkers for diagnosing and predicting cancer progression, and they may also offer new therapeutic targets for treatment.

Our Team

Principal Investigator

RNDr. Vendula Hlaváčková Pospíchalová, Ph.D.

Postdocs

Mgr. Stanislava Sladecek, Ph.D. (2023-

PhD students

Mgr. Šárka Hrachovinová

Master students

Alumni

Phd Students

Mgr. Anna Vyhlídalová Kotrbová, Ph.D. (2022)

Master students

Mgr. Jana Lapinová
Mgr. Jana Kramářová

Collaborations

Coming soon

Grants

2022-2025 National institute for cancer research (LX22NPO5102), Ministry of Education, Youth and Sports of the CR / national recovery plan
2024 Prognostic significance of new biomarkers identified by analysis of extracellular vesicles isolated from ascites in patients with ovarian cance (MUNI/LF-SUp/1350/2023),
Masaryk University
2024 YIP Cancer Sectoral Meeting EMBO (1204/2024),
EMBO (European Molecular Biology Organization) / Funding for conferences and training
2021-2024 Comprehensive genomic profiling in ovarian cancer patients treated with platinumbased chemotherapy: identification of predictive biomarkers and evaluation of the potential of precision oncology approach (NU21-03-00306),
Ministry of Health of the CR / Ministry of Health Research Programme 2020 – 2026
2021-2023 The potential of ascites in ovarian cancer research (MUNI/R/1225/2021), Masaryk University / Grant Agency of Masaryk University
2019 Význam signální dráhy Wnt v patogenezi ovariálním karcinomu (MUNI/E/0532/2019), Masaryk University / Grant Agency of Masaryk University
2017-2019 Funkční a biochemická analýza extracelulárních váčků z ascitů pacientek s karcinomem vaječníku (GJ17-11776Y), Czech Science Foundation / Junior projects
2018 TEM ExosomeAnalyzer: Nový software pro kvantitativní charakterizaci extracelulárních vesikulů pomocí transmisní elektronové mikroskopie (MUNI/E/0876/2018), Masaryk University / Grant Agency of Masaryk University
2014-2016 Automatizovaná analýza elektronmikroskopických snímků pro použití v biologii a medicíně (MUNI/M/1050/2013), Masaryk University / Grant Agency of Masaryk University
2012-2015 Zaměstnáním čerstvých absolventů doktorského studia k vědecké excelenci (CZ.1.07/2.3.00/30.0009), Ministry of Education, Youth and Sports of the CR / Operational Programme Education for Competitiveness

Selected Publications

Vyhlídalová Kotrbová A, Gömöryová K, Mikulová A, Plešingerová H, Sladeček S, Kravec M, Hrachovinová Š, Potěšil D, Dunsmore G, Blériot C, Bied M, Kotouček J, Bednaříková M, Hausnerová J, Minář L, Crha I, Felsinger M, Zdráhal Z, Ginhoux F, Weinberger V, Bryja V, Pospíchalová V. Proteomic analysis of ascitic extracellular vesicles describes tumour microenvironment and predicts patient survival in ovarian cancer. J Extracell Vesicles. 2024 Mar;13(3):e12420. doi: 10.1002/jev2.12420. PMID: 38490958; PMCID: PMC10942866.
Bied M, Pospíchalová V, Blériot C. Circulating extracellular vesicles as the source of diagnostic biomarkers for diseases. Clinical & Translational Discovery. 2022; 2:e145. doi.org/10.1002/ctd2.145
Kotrbová A, Ovesná P, Gybel’ T, Radaszkiewicz T, Bednaříková M, Hausnerová J, Jandáková E, Minář L, Crha I, Weinberger V, Záveský L, Bryja V, Pospíchalová V. WNT signaling inducing activity in ascites predicts poor outcome in ovarian cancer. Theranostics. 2020 Jan 1;10(2):537-552. doi: 10.7150/thno.37423. PMID: 31903136; PMCID: PMC6929979.
Pospichalova V, Svoboda J, Dave Z, Kotrbova A, Kaiser K, Klemova D, Ilkovics L, Hampl A, Crha I, Jandakova E, Minar L, Weinberger V, Bryja V. Simplified protocol for flow cytometry analysis of fluorescently labeled exosomes and microvesicles using dedicated flow cytometer. J Extracell Vesicles. 2015 Mar 31;4:25530. doi: 10.3402/jev.v4.25530. PMID: 25833224; PMCID: PMC4382613.
Drápela S, Kvokačková B, Slabáková E, Kotrbová A, Gömöryová K, Fedr R, Kurfürstová D, Eliáš M, Študent V Jr, Lenčéšová F, Ranjani GS, Pospíchalová V, Bryja V, van Weerden WM, Puhr M, Culig Z, Bouchal J, Souček K. Pre-existing cell subpopulations in primary prostate cancer tumors display surface fingerprints of docetaxel-resistant cells. Cell Oncol (Dordr). 2024 Aug 20. doi: 10.1007/s13402-024-00982-2. Epub ahead of print. PMID: 39162992.
Kotrbová A, Štěpka K, Maška M, Pálenik JJ, Ilkovics L, Klemová D, Kravec M, Hubatka F, Dave Z, Hampl A, Bryja V, Matula P, Pospíchalová V. TEM ExosomeAnalyzer: a computer-assisted software tool for quantitative evaluation of extracellular vesicles in transmission electron microscopy images. J Extracell Vesicles. 2019 Jan 21;8(1):1560808. doi: 10.1080/20013078.2018.1560808. PMID: 30719239; PMCID: PMC6346710.
Mo L, Pospichalova V, Huang Z, Murphy SK, Payne S, Wang F, Kennedy M, Cianciolo GJ, Bryja V, Pizzo SV, Bachelder RE. Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells. PLoS One. 2015 Jul 6;10(7):e0131579. doi: 10.1371/journal.pone.0131579. PMID: 26148191; PMCID: PMC4493087.
Ekumi KM, Paculova H, Lenasi T, Pospichalova V, Bösken CA, Rybarikova J, Bryja V, Geyer M, Blazek D, Barboric M. Ovarian carcinoma CDK12 mutations misregulate expression of DNA repair genes via deficient formation and function of the Cdk12/CycK complex. Nucleic Acids Res. 2015 Mar 11;43(5):2575-89. doi: 10.1093/nar/gkv101. Epub 2015 Feb 20. PMID: 25712099; PMCID: PMC4357706.
Kríz V, Pospíchalová V, Masek J, Kilander MB, Slavík J, Tanneberger K, Schulte G, Machala M, Kozubík A, Behrens J, Bryja V. β-arrestin promotes Wnt-induced low density lipoprotein receptor-related protein 6 (Lrp6) phosphorylation via increased membrane recruitment of Amer1 protein. J Biol Chem. 2014 Jan 10;289(2):1128-41. doi: 10.1074/jbc.M113.498444. Epub 2013 Nov 21. PMID: 24265322; PMCID: PMC3887180.