Proteomic analysis of ascitic extracellular vesicles describes tumour microenvironment and predicts patient survival in ovarian cancer
Language English Country United States Media print
Document type Journal Article
Grant support
MUNI/R/1225/2021
Grant Agency of Masaryk University
LX22NPO5102
European Union-Next Generation EU
NU21-03-00306
Ministry of Health of the Czech Republic
PubMed
38490958
PubMed Central
PMC10942866
DOI
10.1002/jev2.12420
Knihovny.cz E-resources
- Keywords
- ascites, extracellular vesicles (EV), fallopian tube and peritoneum (HGSC), high-grade serous carcinoma of the ovary, macrophage, ovarian cancer (OC), tandem mass spectrometry (MS/MS), tumour microenvironment (TME),
- MeSH
- Ascites metabolism pathology MeSH
- Extracellular Vesicles * metabolism MeSH
- Humans MeSH
- Tumor Microenvironment MeSH
- Ovarian Neoplasms * diagnosis MeSH
- Proteomics MeSH
- Cystadenocarcinoma, Serous * diagnosis genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
High-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies. Many HGSC patients have excess fluid in the peritoneum called ascites. Ascites is a tumour microenvironment (TME) containing various cells, proteins and extracellular vesicles (EVs). We isolated EVs from patients' ascites by orthogonal methods and analyzed them by mass spectrometry. We identified not only a set of 'core ascitic EV-associated proteins' but also defined their subset unique to HGSC ascites. Using single-cell RNA sequencing data, we mapped the origin of HGSC-specific EVs to different types of cells present in ascites. Surprisingly, EVs did not come predominantly from tumour cells but from non-malignant cell types such as macrophages and fibroblasts. Flow cytometry of ascitic cells in combination with analysis of EV protein composition in matched samples showed that analysis of cell type-specific EV markers in HGSC has more substantial prognostic potential than analysis of ascitic cells. To conclude, we provide evidence that proteomic analysis of EVs can define the cellular composition of HGSC TME. This finding opens numerous avenues both for a better understanding of EV's role in tumour promotion/prevention and for improved HGSC diagnostics.
Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic
Department of Health Sciences Faculty of Medicine Masaryk University Brno Czech Republic
Department of Pharmacology and Toxicology Veterinary Research Institute Brno Czech Republic
See more in PubMed
Askeland, A. , Borup, A. , Østergaard, O. , Olsen, J. V. , Lund, S. M. , Christiansen, G. , Kristensen, S. R. , Heegaard, N. H. H. , & Pedersen, S. (2020). Mass‐spectrometry based proteome comparison of extracellular vesicle isolation methods: Comparison of ME‐kit, size‐exclusion chromatography, and high‐speed centrifugation. Biomedicines, 8(8), 246. 10.3390/BIOMEDICINES8080246 PubMed DOI PMC
Azkargorta, M. , Iloro, I. , Escobes, I. , Cabrera, D. , Falcon‐Perez, J. M. , Elortza, F. , & Royo, F. (2021). Human serum extracellular vesicle proteomic profile depends on the enrichment method employed. International Journal of Molecular Sciences, 22(20), 11144. 10.3390/ijms222011144 PubMed DOI PMC
Bakdash, J. Z. , & Marusich, L. R. (2017). Repeated measures correlation. Frontiers in Psychology, 8(MAR), 456. 10.3389/FPSYG.2017.00456/BIBTEX PubMed DOI PMC
Bortot, B. , Apollonio, M. , Rampazzo, E. , Valle, F. , Brucale, M. , Ridolfi, A. , Ura, B. , Addobbati, R. , di Lorenzo, G. , Romano, F. , Buonomo, F. , Ripepi, C. , Ricci, G. , & Biffi, S. (2021). Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix. Molecular Oncology, 15(12), 3596–3614. 10.1002/1878-0261.13110 PubMed DOI PMC
Brennan, K. , Martin, K. , FitzGerald, S. P. , O'Sullivan, J. , Wu, Y. , Blanco, A. , Richardson, C. , & Mc Gee, M. M. (2020). A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum. Scientific Reports, 10(1), 1039. 10.1038/s41598-020-57497-7 PubMed DOI PMC
Cai, J. , Gong, L. , Li, G. , Guo, J. , Yi, X. , & Wang, Z. (2021). Exosomes in ovarian cancer ascites promote epithelial–mesenchymal transition of ovarian cancer cells by delivery of miR‐6780b‐5p. Cell Death and Disease, 12(2), 210. 10.1038/s41419-021-03490-5 PubMed DOI PMC
Chakarov, S. , Lim, H. Y. , Tan, L. , Lim, S. Y. , See, P. , Lum, J. , Zhang, X. M. , Foo, S. , Nakamizo, S. , Duan, K. , Kong, W. T. , Gentek, R. , Balachander, A. , Carbajo, D. , Bleriot, C. , Malleret, B. , Tam, J. K. C. , Baig, S. , Shabeer, M. , … Ginhoux, F. (2019). Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches. Science, 363(6432), eaau0964. 10.1126/science.aau0964 PubMed DOI
Cox, J. , & Mann, M. (2008). MaxQuant enables high peptide identification rates, individualized p.p.b.‐range mass accuracies and proteome‐wide protein quantification. Nature Biotechnology, 26(12), 1367–1372. 10.1038/nbt.1511 PubMed DOI
Cox, J. , Neuhauser, N. , Michalski, A. , Scheltema, R. A. , Olsen, J. V. , & Mann, M. (2011). Andromeda: A peptide search engine integrated into the MaxQuant environment. Journal of Proteome Research, 10(4), 1794–1805. 10.1021/pr101065j PubMed DOI
Cui, Y. , Wu, F. , Tian, D. , Wang, T. , Lu, T. , Huang, X. , Zhang, P. , & Qin, L. (2018). MiR‐199a‐3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8. Oncology Reports, 39(4), 1649–1657. 10.3892/or.2018.6259 PubMed DOI PMC
Dong, L. , Zieren, R. C. , Horie, K. , Kim, C. J. , Mallick, E. , Jing, Y. , Feng, M. , Kuczler, M. D. , Green, J. , Amend, S. R. , Witwer, K. W. , de Reijke, T. M. , Cho, Y. K. , Pienta, K. J. , & Xue, W. (2020). Comprehensive evaluation of methods for small extracellular vesicles separation from human plasma, urine and cell culture medium. Journal of Extracellular Vesicles, 10(2), e12044. 10.1002/jev2.12044 PubMed DOI PMC
Ford, C. E. , Werner, B. , Hacker, N. F. , & Warton, K. (2020). The untapped potential of ascites in ovarian cancer research and treatment. British Journal of Cancer, 123(1), 9–16. 10.1038/s41416-020-0875-x PubMed DOI PMC
Gillespie, M. , Jassal, B. , Stephan, R. , Milacic, M. , Rothfels, K. , Senff‐Ribeiro, A. , Griss, J. , Sevilla, C. , Matthews, L. , Gong, C. , Deng, C. , Varusai, T. , Ragueneau, E. , Haider, Y. , May, B. , Shamovsky, V. , Weiser, J. , Brunson, T. , Sanati, N. , … D'Eustachio, P. (2022). The reactome pathway knowledgebase 2022. Nucleic Acids Research, 50(D1), D687–D692. 10.1093/nar/gkab1028 PubMed DOI PMC
Go, C. D. , Knight, J. D. R. , Rajasekharan, A. , Rathod, B. , Hesketh, G. G. , Abe, K. T. , Youn, J. Y. , Samavarchi‐Tehrani, P. , Zhang, H. , Zhu, L. Y. , Popiel, E. , Lambert, J. P. , Coyaud, É. , Cheung, S. W. T. , Rajendran, D. , Wong, C. J. , Antonicka, H. , Pelletier, L. , Palazzo, A. F. , … Gingras, A. C. (2021). A proximity‐dependent biotinylation map of a human cell. Nature, 595(7865), 120–124. 10.1038/s41586-021-03592-2 PubMed DOI
He, J. , Liu, Y. , Zhang, L. , & Zhang, H. (2018). Integrin subunit beta 8 (ITGB8) upregulation is an independent predictor of unfavorable survival of high‐grade serous ovarian carcinoma patients. Medical Science Monitor, 24, 8933–8940. 10.12659/MSM.911518 PubMed DOI PMC
Holcar, M. , Kandušer, M. , & Lenassi, M. (2021). Blood nanoparticles—Influence on extracellular vesicle isolation and characterization. Frontiers in Pharmacology, 12, 773844. 10.3389/fphar.2021.773844 PubMed DOI PMC
Hoshino, A. , Kim, H. S. , Bojmar, L. , Gyan, K. E. , Cioffi, M. , Hernandez, J. , Zambirinis, C. P. , Rodrigues, G. , Molina, H. , Heissel, S. , Mark, M. T. , Steiner, L. , Benito‐Martin, A. , Lucotti, S. , di Giannatale, A. , Offer, K. , Nakajima, M. , Williams, C. , Nogués, L. , … Lyden, D. (2020). Extracellular vesicle and particle biomarkers define multiple human cancers. Cell, 182(4), 1044–1061.e18. 10.1016/j.cell.2020.07.009 PubMed DOI PMC
Huddleston, H. G. , Wong, K. K. , Welch, W. R. , Berkowitz, R. S. , & Mok, S. C. (2005). Clinical applications of microarray technology: Creatine kinase B is an up‐regulated gene in epithelial ovarian cancer and shows promise as a serum marker. Gynecologic Oncology, 96(1), 77–83. 10.1016/j.ygyno.2004.08.047 PubMed DOI
Izar, B. , Tirosh, I. , Stover, E. H. , Wakiro, I. , Cuoco, M. S. , Alter, I. , Rodman, C. , Leeson, R. , Su, M. J. , Shah, P. , Iwanicki, M. , Walker, S. R. , Kanodia, A. , Melms, J. C. , Mei, S. , Lin, J. R. , Porter, C. B. M. , Slyper, M. , Waldman, J. , … Regev, A. (2020). A single‐cell landscape of high‐grade serous ovarian cancer. Nature Medicine, 26(8), 1271–1279. 10.1038/s41591-020-0926-0 PubMed DOI PMC
Jo, A. , Green, A. , Medina, J. E. , Iyer, S. , Ohman, A. W. , McCarthy, E. T. , Reinhardt, F. , Gerton, T. , Demehin, D. , Mishra, R. , Kolin, D. L. , Zheng, H. , Cheon, J. , Crum, C. P. , Weinberg, R. A. , Rueda, B. R. , Castro, C. M. , Dinulescu, D. M. , & Lee, H. (2023). Inaugurating high‐throughput profiling of extracellular vesicles for earlier ovarian cancer detection. Advanced Science, 10(27), e2301930. 10.1002/advs.202301930 PubMed DOI PMC
Kajiyama, H. , Shibata, K. , Ino, K. , Mizutani, S. , Nawa, A. , & Kikkawa, F. (2010). The expression of dipeptidyl peptidase IV (DPPIV/CD26) is associated with enhanced chemosensitivity to paclitaxel in epithelial ovarian carcinoma cells. Cancer Science, 101(2), 347–354. 10.1111/j.1349-7006.2009.01378.x PubMed DOI PMC
Karimi, N. , Cvjetkovic, A. , Jang, S. C. , Crescitelli, R. , Hosseinpour Feizi, M. A. , Nieuwland, R. , Lötvall, J. , & Lässer, C. (2018). Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins. Cellular and Molecular Life Sciences, 75(15), 2873–2886. 10.1007/s00018-018-2773-4 PubMed DOI PMC
Kipps, E. , Tan, D. S. , & Kaye, S. B. (2013). Meeting the challenge of ascites in ovarian cancer: new avenues for therapy and research. Nature Reviews Cancer, 13(4), 273–282. 10.1038/nrc3432 PubMed DOI PMC
Kosowska, A. , Garczorz, W. , Kłych‐Ratuszny, A. , Aghdam, M. R. F. , Kimsa‐Furdzik, M. , Simka‐Lampa, K. , & Francuz, T. (2020). Sitagliptin modulates the response of ovarian cancer cells to chemotherapeutic agents. International Journal of Molecular Sciences, 21(23), 8976. 10.3390/ijms21238976 PubMed DOI PMC
Kotrbová, A. , Štěpka, K. , Maška, M. , Pálenik, J. J. , Ilkovics, L. , Klemová, D. , Kravec, M. , Hubatka, F. , Dave, Z. , Hampl, A. , Bryja, V. , Matula, P. , & Pospíchalová, V. (2019). TEM ExosomeAnalyzer: A computer‐assisted software tool for quantitative evaluation of extracellular vesicles in transmission electron microscopy images. Journal of Extracellular Vesicles, 8(1), 1560808. 10.1080/20013078.2018.1560808 PubMed DOI PMC
Li, J. , Li, Y. , Li, Q. , Sun, L. , Tan, Q. , Zheng, L. , Lu, Y. , Zhu, J. , Qu, F. , & Tan, W. (2023). An aptamer‐based nanoflow cytometry method for the molecular detection and classification of ovarian cancers through profiling of tumor markers on small extracellular vesicles. Angewandte Chemie (International Ed. in English), 63, e202314262. 10.1002/anie.202314262 PubMed DOI
Li, X. H. , Chen, X. J. , Ou, W. B. , Zhang, Q. , Lv, Z. R. , Zhan, Y. , Ma, L. , Huang, T. , Yan, Y. B. , & Zhou, H. M. (2013). Knockdown of creatine kinase B inhibits ovarian cancer progression by decreasing glycolysis. International Journal of Biochemistry and Cell Biology, 45(5), 979–986. 10.1016/j.biocel.2013.02.003 PubMed DOI
Li, Y. , Zhou, J. , Zhuo, Q. , Zhang, J. , Xie, J. , Han, S. , & Zhao, S. (2019). Malignant ascite‐derived extracellular vesicles inhibit T cell activity by upregulating Siglec‐10 expression. Cancer Management and Research, 11, 7123–7134. 10.2147/CMAR.S210568 PubMed DOI PMC
Lischnig, A. , Bergqvist, M. , Ochiya, T. , & Lässer, C. (2022). Quantitative proteomics identifies proteins enriched in large and small extracellular vesicles. Molecular and Cellular Proteomics, 21(9), 100273. 10.1016/j.mcpro.2022.100273 PubMed DOI PMC
Lucotti, S. , Kenific, C. M. , Zhang, H. , & Lyden, D. (2022). Extracellular vesicles and particles impact the systemic landscape of cancer. The EMBO Journal, 41(18), e109288. 10.15252/embj.2021109288 PubMed DOI PMC
Mitra, A. , Yoshida‐Court, K. , Solley, T. N. , Mikkelson, M. , Yeung, C. L. A. , Nick, A. , Lu, K. , & Klopp, A. H. (2021). Extracellular vesicles derived from ascitic fluid enhance growth and migration of ovarian cancer cells. Scientific Reports, 11(1), 9149. 10.1038/s41598-021-88163-1 PubMed DOI PMC
Noren Hooten, N. , Byappanahalli, A. M. , Vannoy, M. , Omoniyi, V. , & Evans, M. K. (2022). Influences of age, race, and sex on extracellular vesicle characteristics. Theranostics, 12(9), 4459–4476. 10.7150/thno.72676 PubMed DOI PMC
Patil, A. , & Patil, A. (2022). CellKb immune: A manually curated database of mammalian hematopoietic marker gene sets for rapid cell type identification . 10.1101/2020.12.01.389890 DOI
Perez‐Riverol, Y. , Bai, J. , Bandla, C. , García‐Seisdedos, D. , Hewapathirana, S. , Kamatchinathan, S. , Kundu, D. J. , Prakash, A. , Frericks‐Zipper, A. , Eisenacher, M. , Walzer, M. , Wang, S. , Brazma, A. , & Vizcaíno, J. A. (2022). The PRIDE database resources in 2022: A hub for mass spectrometry‐based proteomics evidences. Nucleic Acids Research, 50(D1), D543–D552. 10.1093/NAR/GKAB1038 PubMed DOI PMC
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. (2015). Simplified protocol for flow cytometry analysis of fluorescently labeled exosomes and microvesicles using dedicated flow cytometer. Journal of Extracellular Vesicles, 4, 25530. 10.3402/jev.v4.25530 PubMed DOI PMC
Rakina, M. , Kazakova, A. , Villert, A. , Kolomiets, L. , & Larionova, I. (2022). Spheroid formation and peritoneal metastasis in ovarian cancer: The role of stromal and immune components. International Journal of Molecular Sciences, 23(11), 6215. 10.3390/ijms23116215 PubMed DOI PMC
Rickard, B. P. , Conrad, C. , Sorrin, A. J. , Ruhi, M. K. , Reader, J. C. , Huang, S. A. , Franco, W. , Scarcelli, G. , Polacheck, W. J. , Roque, D. M. , del Carmen, M. G. , Huang, H. C. , Demirci, U. , & Rizvi, I. (2021). Malignant ascites in ovarian cancer: Cellular, acellular, and biophysical determinants of molecular characteristics and therapy response. Cancers, 13(17), 4318. 10.3390/cancers13174318 PubMed DOI PMC
Ritch, S. J. , & Telleria, C. M. (2022). The transcoelomic ecosystem and epithelial ovarian cancer dissemination. Frontiers in Endocrinology, 13, 886533. 10.3389/fendo.2022.886533 PubMed DOI PMC
Siegel, R. L. , Miller, K. D. , Wagle, N. S. , & Jemal, A. (2023). Cancer statistics, 2023. CA: A Cancer Journal for Clinicians, 73(1), 17–48. 10.3322/caac.21763 PubMed DOI
Stejskal, K. , Potěšil, D. , & Zdráhal, Z. (2013). Suppression of peptide sample losses in autosampler vials. Journal of Proteome Research, 12(6), 3057–3062. 10.1021/pr400183v PubMed DOI
Sung, H. , Ferlay, J. , Siegel, R. L. , Laversanne, M. , Soerjomataram, I. , Jemal, A. , & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. 10.3322/caac.21660 PubMed DOI
Takov, K. , Yellon, D. M. , & Davidson, S. M. (2019). Comparison of small extracellular vesicles isolated from plasma by ultracentrifugation or size‐exclusion chromatography: Yield, purity and functional potential. Journal of Extracellular Vesicles, 8(1), 1560809. 10.1080/20013078.2018.1560809 PubMed DOI PMC
Ter‐Ovanesyan, D. , Norman, M. , Lazarovits, R. , Trieu, W. , Lee, J. H. , Church, G. M. , & Walt, D. R. (2021). Framework for rapid comparison of extracellular vesicle isolation methods. ELife, 10, e70725. 10.7554/eLife.70725 PubMed DOI PMC
Théry, C. , Witwer, K. W. , Aikawa, E. , Alcaraz, M. J. , Anderson, J. D. , Andriantsitohaina, R. , Antoniou, A. , Arab, T. , Archer, F. , Atkin‐Smith, G. K. , Ayre, D. C. , Bach, J. M. , Bachurski, D. , Baharvand, H. , Balaj, L. , Baldacchino, S. , Bauer, N. N. , Baxter, A. A. , Bebawy, M. , … Zuba‐Surma, E. K. (2018). Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. Journal of Extracellular Vesicles, 7(1), 1535750. 10.1080/20013078.2018.1535750 PubMed DOI PMC
Tian, Y. , Gong, M. , Hu, Y. , Liu, H. , Zhang, W. , Zhang, M. , Hu, X. , Aubert, D. , Zhu, S. , Wu, L. , & Yan, X. (2020). Quality and efficiency assessment of six extracellular vesicle isolation methods by nano‐flow cytometry. Journal of Extracellular Vesicles, 9(1), 1697028. 10.1080/20013078.2019.1697028 PubMed DOI PMC
Van Deun, J. , Mestdagh, P. , Agostinis, P. , Akay, Ö. , Anand, S. , Anckaert, J. , Martinez, Z. A. , Baetens, T. , Beghein, E. , Bertier, L. , Berx, G. , Boere, J. , Boukouris, S. , Bremer, M. , Buschmann, D. , Byrd, J. B. , Casert, C. , Cheng, L. , Cmoch, A. , … Hendrix, A. (2017). EV‐TRACK: Transparent reporting and centralizing knowledge in extracellular vesicle research. Nature Methods, 14(3), 228–232. 10.1038/nmeth.4185 PubMed DOI
Veerman, R. E. , Teeuwen, L. , Czarnewski, P. , Güclüler Akpinar, G. , Sandberg, A. S. , Cao, X. , Pernemalm, M. , Orre, L. M. , Gabrielsson, S. , & Eldh, M. (2021). Molecular evaluation of five different isolation methods for extracellular vesicles reveals different clinical applicability and subcellular origin. Journal of Extracellular Vesicles, 10(9), e12128. 10.1002/jev2.12128 PubMed DOI PMC
Vergauwen, G. , Tulkens, J. , Pinheiro, C. , Avila Cobos, F. , Dedeyne, S. , de Scheerder, M. A. , Vandekerckhove, L. , Impens, F. , Miinalainen, I. , Braems, G. , Gevaert, K. , Mestdagh, P. , Vandesompele, J. , Denys, H. , de Wever, O. , & Hendrix, A. (2021). Robust sequential biophysical fractionation of blood plasma to study variations in the biomolecular landscape of systemically circulating extracellular vesicles across clinical conditions. Journal of Extracellular Vesicles, 10(10), e12122. 10.1002/jev2.12122 PubMed DOI PMC
Wang, W. , Jo, H. , Park, S. , Kim, H. , Kim, S. I. , Han, Y. , Lee, J. , Seol, A. , Kim, J. , Lee, M. , Lee, C. , Dhanasekaran, D. N. , Ahn, T. , & Song, Y. S. (2022). Integrated analysis of ascites and plasma extracellular vesicles identifies a miRNA‐based diagnostic signature in ovarian cancer. Cancer Letters, 542, 215735. 10.1016/j.canlet.2022.215735 PubMed DOI
Wei, M. , Bai, X. , & Dong, Q. (2022). Identification of novel candidate genes and small molecule drugs in ovarian cancer by bioinformatics strategy. Translational Cancer Research, 11(6), 1630–1643. 10.21037/tcr-21-2890 PubMed DOI PMC
Wei, R. , Zhao, L. , Kong, G. , Liu, X. , Zhu, S. , Zhang, S. , & Min, L. (2020). Combination of size‐exclusion chromatography and ultracentrifugation improves the proteomic profiling of plasma‐derived small extracellular vesicles. Biological Procedures Online, 22(1), 12. 10.1186/s12575-020-00125-5 PubMed DOI PMC
Wilson, A. L. , Moffitt, L. R. , Wilson, K. L. , Bilandzic, M. , Wright, M. D. , Gorrell, M. D. , Oehler, M. K. , Plebanski, M. , & Stephens, A. N. (2021). DPP4 inhibitor sitagliptin enhances lymphocyte recruitment and prolongs survival in a syngeneic ovarian cancer mouse model. Cancers, 13(3), 487. 10.3390/cancers13030487 PubMed DOI PMC
Wiśniewski, J. R. , Ostasiewicz, P. , & Mann, M. (2011). High recovery FASP applied to the proteomic analysis of microdissected formalin fixed paraffin embedded cancer tissues retrieves known colon cancer markers. Journal of Proteome Research, 10(7), 3040–3049. 10.1021/pr200019m PubMed DOI
Yokoi, A. , Ukai, M. , Yasui, T. , Inokuma, Y. , Hyeon‐Deuk, K. , Matsuzaki, J. , Yoshida, K. , Kitagawa, M. , Chattrairat, K. , Iida, M. , Shimada, T. , Manabe, Y. , Chang, I. Y. , Asano‐Inami, E. , Koya, Y. , Nawa, A. , Nakamura, K. , Kiyono, T. , Kato, T. , … Kajiyama, H. (2023). Identifying high‐grade serous ovarian carcinoma‐ specific extracellular vesicles by polyketone‐coated nanowires. Science Advances, 9(27), eade6958. 10.1126/sciadv.ade6958 PubMed DOI PMC
Zheng, X. , Wang, X. , Cheng, X. , Liu, Z. , Yin, Y. , Li, X. , Huang, Z. , Wang, Z. , Guo, W. , Ginhoux, F. , Li, Z. , Zhang, Z. , & Wang, X. (2023). Single‐cell analyses implicate ascites in remodeling the ecosystems of primary and metastatic tumors in ovarian cancer. Nature Cancer, 4(8), 1138–1156. 10.1038/s43018-023-00599-8 PubMed DOI PMC