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Journal of Cancer Research and Clinical Oncology

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09.10.2019 | Original Article – Cancer Research

Malignant ascites-derived organoid (MADO) cultures for gastric cancer in vitro modelling and drug screening

verfasst von: Jie Li, Huawei Xu, Lixing Zhang, Lele Song, Dan Feng, Xiaobo Peng, Meihong Wu, Yang Zou, Bin Wang, Lixing Zhan, Guoqiang Hua, Xianbao Zhan

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 11/2019

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Abstract

Purpose

Malignant ascites (MA) is a common manifestation in advanced gastric cancer with peritoneal carcinomatosis and usually indicates a poor prognosis. However, lack of in vitro models that can faithfully recapitulate the characteristics of tumour cells in ascites hinders related researches. Tumour organoids have emerged as a robust in vitro model for tumour research and drug screening. Hence, we aimed to generate a 3-D in vitro organoid cultures from malignant ascites of gastric cancer for disease modelling and drug screening.

Methods

Eleven MADOs were generated from the MA tumour cells of gastric cancer patients. We made comparisons between MADOs and original MA tumour cells in histopathology by immunohistochemistry and genomics by whole-exome sequencing. In order to evaluate MADOs as functional in vitro disease models, we tested whether MADOs could be used for drug sensitivity screens.

Results

Eleven MADO cultures from human gastric cancer were established. MADOs demonstrated divergent growth characteristics and morphologies. MADO cultures preserve the histological architecture, genomic landscape of the corresponding MA tumour cells. MADOs exhibited heterogeneous responses to standard-of-care chemotherapeutics.

Conclusions

We generated MADOs modelling characteristics and mutated genes of MA tumour cells. A broad range of intrinsic MADO response to conventional chemotherapeutics suggests MADOs are amenable to drug screening.

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Ajani JA, D’Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, Denlinger CS, Fanta P, Farjah F, Fuchs CS et al (2016) Gastric cancer, version 3.2016, NCCN clinical practice guidelines in oncology. J Nat Compr Cancer Netw 14:1286–1312CrossRef

Barni S, Cabiddu M, Ghilardi M, Petrelli F (2011) A novel perspective for an orphan problem: old and new drugs for the medical management of malignant ascites. Crit Rev Oncol Hematol 79:144–153PubMedCrossRef

Bartfeld S, Bayram T, van de Wetering M, Huch M, Begthel H, Kujala P, Vries R, Peters PJ, Clevers H (2015) In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148(126–136):e126CrossRef

Boeva V, Popova T, Bleakley K, Chiche P, Cappo J, Schleiermacher G, Janoueix-Lerosey I, Delattre O, Barillot E (2012) Control-FREEC: a tool for assessing copy number and allelic content using next-generation sequencing data. Bioinform (Oxf Engl) 28:423–425CrossRef

Boj SF, Hwang CI, Baker LA, Chio II, Engle DD, Corbo V, Jager M, Ponz-Sarvise M, Tiriac H, Spector MS et al (2015) Organoid models of human and mouse ductal pancreatic cancer. Cell 160:324–338PubMedCrossRef

Broutier L, Mastrogiovanni G, Verstegen MM, Francies HE, Gavarro LM, Bradshaw CR, Allen GE, Arnes-Benito R, Sidorova O, Gaspersz MP et al (2017) Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med 23:1424–1435PubMedPubMedCentralCrossRef

Cancer Genome Atlas Research, N (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202–209CrossRef

Cavazzoni E, Bugiantella W, Graziosi L, Franceschini MS, Donini A (2013) Malignant ascites: pathophysiology and treatment. Int J Clin Oncol 18:1–9PubMedCrossRef

Cibulskis K, Lawrence MS, Carter SL, Sivachenko A, Jaffe D, Sougnez C, Gabriel S, Meyerson M, Lander ES, Getz G (2013) Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol 31:213–219PubMedPubMedCentralCrossRef

Cristescu R, Lee J, Nebozhyn M, Kim K-M, Ting JC, Wong SS, Liu J, Yue YG, Wang J, Yu K et al (2015) Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med 21:449–456PubMedCrossRef

Fang N, Zhang HQ, He B, Xie M, Lu S, Wan YY, Wang NR (2014) Clinicopathological characteristics and prognosis of gastric cancer with malignant ascites. Tumour Biol 35:3261–3268PubMedCrossRef

Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, Maclntyre MF, Allen C, Hansen G, Woodbrook R, Wolfe C et al (2015) The global burden of cancer 2013 global burden of disease cancer collaboration. JAMA Oncol 1:505–527PubMedCrossRef

Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A, Dowling C, Wanjala JN, Undvall EA, Arora VK et al (2014) Organoid cultures derived from patients with advanced prostate cancer. Cell 159:176–187PubMedPubMedCentralCrossRef

Golan T, Atias D, Barshack I, Avivi C, Goldstein RS, Berger R (2014) Ascites-derived pancreatic ductal adenocarcinoma primary cell cultures as a platform for personalised medicine. Br J Cancer 110:2269–2276PubMedPubMedCentralCrossRef

Hill SJ, Decker B, Roberts EA, Horowitz NS, Muto MG, Worley MJ Jr, Feltmate CM, Nucci MR, Swisher EM, Nguyen H et al (2018) Prediction of DNA repair inhibitor response in short-term patient-derived ovarian cancer organoids. Cancer Discov 8:1404–1421PubMedPubMedCentralCrossRef

Huang L, Holtzinger A, Jagan I, BeGora M, Lohse I, Ngai N, Nostro C, Wang R, Muthuswamy LB, Crawford HC et al (2015) Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids. Nat Med 21:1364–1371PubMedPubMedCentralCrossRef

Jehn CF, Kupferling S, Oskay-Ozcelik G, Luftner D (2015) A survey of treatment approaches of malignant ascites in Germany and Austria. Support Care Cancer 23:2073–2078PubMedCrossRef

Jia W, Zhu Z, Zhang T, Fan G, Fan P, Liu Y, Duan Q (2013) Treatment of malignant ascites with a combination of chemotherapy drugs and intraperitoneal perfusion of verapamil. Cancer Chemother Pharmacol 71:1585–1590PubMedCrossRef

Kobayashi M, Ueyama Y, Nakanishi H, Ishida H, Takahashi E, Nakamura S, Koshikawa T, Yatabe Y (2006) Immunocytochemical detection using CDX2: an aid for discerning tumor involvement in ascites cytology. Cancer 108:114–118PubMedCrossRef

Lane D, Goncharenko-Khaider N, Rancourt C, Piche A (2010) Ovarian cancer ascites protects from TRAIL-induced cell death through alpha v beta 5 integrin-mediated focal adhesion kinase and Akt activation. Oncogene 29:3519–3531PubMedCrossRef

Lee SH, Hu W, Matulay JT, Silva MV, Owczarek TB, Kim K, Chua CW, Barlow LJ, Kandoth C, Williams AB et al (2018) Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell 173:515–528PubMedPubMedCentralCrossRef

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, Genome Project Data Processing S (2009) The sequence alignment/map format and SAMtools. Bioinform (Oxf Engl) 25:2078–2079CrossRef

Li X, Francies HE, Secrier M, Perner J, Miremadi A, Galeano-Dalmau N, Barendt WJ, Letchford L, Leyden GM, Goffin EK et al (2018) Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics. Nat Commun 9:2983PubMedPubMedCentralCrossRef

Maeda H, Kobayashi M, Sakamoto J (2015) Evaluation and treatment of malignant ascites secondary to gastric cancer. World J Gastroenterol 21:10936–10947PubMedPubMedCentralCrossRef

Mateescu, C., Becq, A., Bouattour, M., Dreyer, C., Falvre, S.J., and Raymond, E. (2014). Bevacizumab administered intraperitoneally as palliative treatment of malignant refractory ascites. J Clin Oncol 32:1. https://ascopubs.org/doi/10.1200/jco.2014.32.15_suppl.e20617. Accessed 31 January 2017CrossRef

Mills GB, May C, Hill M, Campbell S, Shaw P, Marks A (1990) Ascitic fluid from human ovarian cancer patients contains growth factors necessary for intraperitoneal growth of human ovarian adenocarcinoma cells. J Clin Investig 86:851–855PubMedPubMedCentralCrossRef

Nanki K, Toshimitsu K, Takano A, Fujii M, Shimokawa M, Ohta Y, Matano M, Seino T, Nishikori S, Ishikawa K et al (2018) Divergent routes toward Wnt and R-spondin niche independency during human gastric carcinogenesis. Cell 174:856–869PubMedCrossRef

Ogawa J, Pao GM, Shokhirev MN, Verma IM (2018) Glioblastoma model using human cerebral organoids. Cell Rep 23:1220–1229PubMedPubMedCentralCrossRef

Ott MG, Marme F, Moldenhauer G, Lindhofer H, Hennig M, Spannagl R, Essing MM, Linke R, Seimetz D (2012) Humoral response to catumaxomab correlates with clinical outcome: results of the pivotal phase II/III study in patients with malignant ascites. Int J Cancer 130:2195–2203PubMedCrossRef

Puiffe ML, Le Page C, Filali-Mouhim A, Zietarska M, Ouellet V, Tonin PN, Chevrette M, Provencher DM, Mes-Masson AM (2007) Characterization of ovarian cancer ascites on cell invasion, proliferation, spheroid formation, and gene expression in an in vitro model of epithelial ovarian cancer. Neoplasia (NY) 9:820–829CrossRef

Randle RW, Swett KR, Swords DS, Shen P, Stewart JH, Levine EA, Votanopoulos KI (2014) Efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in the management of malignant ascites. Ann Surg Oncol 21:1474–1479PubMedCrossRef

Roerink SF, Sasaki N, Lee-Six H, Young MD, Alexandrov LB, Behjati S, Mitchell TJ, Grossmann S, Lightfoot H, Egan DA et al (2018) Intra-tumour diversification in colorectal cancer at the single-cell level. Nature 556:457–462PubMedCrossRef

Sachs N, de Ligt J, Kopper O, Gogola E, Bounova G, Weeber F, Balgobind AV, Wind K, Gracanin A, Begthel H et al (2018) A living biobank of breast cancer organoids captures disease heterogeneity. Cell 172:373–386PubMedCrossRef

Saunders CT, Wong WS, Swamy S, Becq J, Murray LJ, Cheetham RK (2012) Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs. Bioinform (Oxf Engl) 28:1811–1817CrossRef

Schutte M, Risch T, Abdavi-Azar N, Boehnke K, Schumacher D, Keil M, Yildiriman R, Jandrasits C, Borodina T, Amstislavskiy V et al (2017) Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors. Nat Commun 8:14262PubMedPubMedCentralCrossRef

Seidlitz T, Merker SR, Rothe A, Zakrzewski F, von Neubeck C, Grutzmann K, Sommer U, Schweitzer C, Scholch S, Uhlemann H et al (2019) Human gastric cancer modelling using organoids. Gut 68:207–217PubMedCrossRef

Shepherd TG, Thériault BL, Campbell EJ, Nachtigal MW (2007) Primary culture of ovarian surface epithelial cells and ascites-derived ovarian cancer cells from patients. Nat Protoc 1:2643CrossRef

Tiriac H, Belleau P, Engle DD, Plenker D, Deschenes A, Somerville TDD, Froeling FEM, Burkhart RA, Denroche RE, Jang GH et al (2018) Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer Discov 8:1112–1129PubMedPubMedCentralCrossRef

van de Wetering M, Francies H, Francis J, Bounova G, Iorio F, Pronk A, van Houdt W, van Gorp J, Taylor-Weiner A, Kester L et al (2015) Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161:933–945PubMedPubMedCentralCrossRef

Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernandez-Mateos J, Khan K, Lampis A, Eason K, Huntingford I, Burke R et al (2018) Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 359:920–926PubMedPubMedCentralCrossRef

Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38:e164PubMedPubMedCentralCrossRef

Wang K, Yuen ST, Xu J, Lee SP, Yan HH, Shi ST, Siu HC, Deng S, Chu KM, Law S et al (2014) Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet 46:573–582PubMedCrossRef

Weeber F, Ooft SN, Dijkstra KK, Voest EE (2017) Tumor Organoids as a pre-clinical cancer model for drug discovery. Cell Chem Biol 24:1092–1100PubMedCrossRef

Yan HHN, Siu HC, Law S, Ho SL, Yue SSK, Tsui WY, Chan D, Chan AS, Ma S, Lam KO et al (2018) A Comprehensive human gastric cancer organoid biobank captures tumor subtype heterogeneity and enables therapeutic screening. Cell Stem Cell 23:882–897PubMedCrossRef

Zang ZJ, Cutcutache I, Poon SL, Zhang SL, McPherson JR, Tao J, Rajasegaran V, Heng HL, Deng N, Gan A et al (2012) Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes. Nat Genet 44:570–574PubMedCrossRef

Titel: Malignant ascites-derived organoid (MADO) cultures for gastric cancer in vitro modelling and drug screening
verfasst von: Jie Li
Huawei Xu
Lixing Zhang
Lele Song
Dan Feng
Xiaobo Peng
Meihong Wu
Yang Zou
Bin Wang
Lixing Zhan
Guoqiang Hua
Xianbao Zhan
Publikationsdatum: 09.10.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 11/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-03004-z

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Malignant ascites-derived organoid (MADO) cultures for gastric cancer in vitro modelling and drug screening

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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